Voltage-gated calcium channels: Novel targets for cancer therapy

Phan,Nam  Nhut; Wang,Chih‑Yang; Chen,Chien‑Fu; Sun,Zhengda; Lai,Ming‑Derg; Lin,Yen‑Chang

doi:10.3892/ol.2017.6457

Voltage-gated calcium channels: Novel targets for cancer therapy

Authors:
- Nam Nhut Phan
- Chih‑Yang Wang
- Chien‑Fu Chen
- Zhengda Sun
- Ming‑Derg Lai
- Yen‑Chang Lin
View Affiliations

Affiliations: Faculty of Applied Sciences, Ton Duc Thang University, Tan Phong Ward, Ho Chi Minh 700000, Vietnam, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., School of Chinese Medicine for Post‑Baccalaureate, I‑Shou University, Kaohsiung 84001, Taiwan, R.O.C., Department of Radiology, University of California, San Francisco, CA 94143, USA, Graduate Institute of Biotechnology, Chinese Culture University, Taipei 1114, Taiwan, R.O.C.
Published online on: June 22, 2017 https://doi.org/10.3892/ol.2017.6457
Pages: 2059-2074
Copyright: © Phan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Voltage-gated calcium channels (VGCCs) comprise five subtypes: The L‑type; R‑type; N‑type; P/Q‑type; and T‑type, which are encoded by α1 subunit genes. Calcium ion channels also have confirmed roles in cellular functions, including mitogenesis, proliferation, differentiation, apoptosis and metastasis. An association between VGCCs, a reduction in proliferation and an increase in apoptosis in prostate cancer cells has also been reported. Therefore, in the present study, the online clinical database Oncomine was used to identify the alterations in the mRNA expression level of VGCCs in 19 cancer subtypes. Overall, VGCC family genes exhibited under‑expression in numerous types of cancer, including brain, breast, kidney and lung cancers. Notably, the majority of VGCC family members (CACNA1C, CACNA1D, CACNA1A, CACNA1B, CACNA1E, CACNA1H and CACNA1I) exhibited low expression in brain tumors, with mRNA expression levels in the top 1‑9% of downregulated gene rankings. A total of 5 VGCC family members (CACNA1A, CACNA1B, CACNA1E, CACNA1G and CACNA1I) were under‑expressed in breast cancer, with a gene ranking in the top 1‑10% of the low‑expressed genes compared with normal tissue. In kidney and lung cancers, CACNA1S, CACNA1C, CACNA1D, CACNA1A and CACNA1H exhibited low expression, with gene rankings in the top 1‑8% of downregulated genes. In conclusion, the present findings may contribute to the development of new cancer treatment approaches by identifying target genes involved in specific types of cancer.

View Figures

View References

1	Sarkar P and Kumar S: Calcium sensing receptor modulation for cancer therapy. Asian Pac J Cancer Prev. 13:3561–3568. 2012. View Article : Google Scholar : PubMed/NCBI
2	Lang F, Föller M, Lang KS, Lang PA, Ritter M, Gulbins E, Vereninov A and Huber SM: Ion channels in cell proliferation and apoptotic cell death. J Membr Biol. 205:147–157. 2005. View Article : Google Scholar : PubMed/NCBI
3	Cuddapah VA and Sontheimer H: Ion channels and tranporters [corrected] in cancer. 2. Ion channels and the control of cancer cell migration. Am J Physiol Cell Physiol. 301:C541–C549. 2011. View Article : Google Scholar : PubMed/NCBI
4	Long J, Zhang ZB, Liu Z, Xu YH and Ge CL: Loss of heterozygosity at the calcium regulation gene locus on chromosome 10q in human pancreatic cancer. Asian Pac J Cancer Prev. 16:2489–2493. 2015. View Article : Google Scholar : PubMed/NCBI
5	Azimi I, Roberts-Thomson SJ and Monteith GR: Calcium influx pathways in breast cancer: Opportunities for pharmacological intervention. Br J Pharmacol. 171:945–960. 2014. View Article : Google Scholar : PubMed/NCBI
6	Loughlin KR: Calcium channel blockers and prostate cancer. Urol Oncol. 32:537–538. 2014. View Article : Google Scholar : PubMed/NCBI
7	Chen Q, Zhang Q, Zhong F, Guo S, Jin Z, Shi W, Chen C and He J: Association between calcium channel blockers and breast cancer: A meta-analysis of observational studies. Pharmacoepidemiol Drug Saf. 23:711–718. 2014. View Article : Google Scholar : PubMed/NCBI
8	George GP, Ramesh V and Mittal RD: Impact of total and ionized serum calcium on prostate cancer risk in North Indian men. Asian Pac J Cancer Prev. 12:1257–1260. 2011.PubMed/NCBI
9	Mahmoudi T, Karimi K, Arkani M, Farahani H, Nobakht H, Dabiri R, Asadi A and Zali MR: Parathyroid hormone gene rs6256 and calcium sensing receptor gene rs1801725 variants are not associated with susceptibility to colorectal cancer in Iran. Asian Pac J Cancer Prev. 15:6035–6039. 2014. View Article : Google Scholar : PubMed/NCBI
10	Stegmaier K, Ross KN, Colavito SA, O'Malley S, Stockwell BR and Golub TR: Gene expression-based high-throughput screening (GE-HTS) and application to leukemia differentiation. Nat Genet. 36:257–263. 2004. View Article : Google Scholar : PubMed/NCBI
11	Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, Kim JY, Goumnerova LC, Black PM, Lau C, et al: Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 415:436–442. 2002. View Article : Google Scholar : PubMed/NCBI
12	Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP, Quist MJ, Jing X, Lonigro RJ, Brenner JC, et al: The mutational landscape of lethal castration-resistant prostate cancer. Nature. 487:239–243. 2012. View Article : Google Scholar : PubMed/NCBI
13	Storz MN, van de Rijn M, Kim YH, Mraz-Gernhard S, Hoppe RT and Kohler S: Gene expression profiles of cutaneous B cell lymphoma. J Invest Dermatol. 120:865–870. 2003. View Article : Google Scholar : PubMed/NCBI
14	Bonome T, Levine DA, Shih J, Randonovich M, Pise-Masison CA, Bogomolniy F, Ozbun L, Brady J, Barrett JC, Boyd J and Birrer MJ: A gene signature predicting for survival in suboptimally debulked patients with ovarian cancer. Cancer Res. 68:5478–5486. 2008. View Article : Google Scholar : PubMed/NCBI
15	Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, et al: Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy. Nat Genet. 42:715–721. 2010. View Article : Google Scholar : PubMed/NCBI
16	Skotheim RI, Lind GE, Monni O, Nesland JM, Abeler VM, Fosså SD, Duale N, Brunborg G, Kallioniemi O, Andrews PW and Lothe RA: Differentiation of human embryonal carcinomas in vitro and in vivo reveals expression profiles relevant to normal development. Cancer Res. 65:5588–5598. 2005. View Article : Google Scholar : PubMed/NCBI
17	Cutcliffe C, Kersey D, Huang CC, Zeng Y, Walterhouse D and Perlman EJ; Renal Tumor Committee of the Children's Oncology Group, : Clear cell sarcoma of the kidney: Up-regulation of neural markers with activation of the sonic hedgehog and Akt pathways. Clin Cancer Res. 11:7986–7994. 2005. View Article : Google Scholar : PubMed/NCBI
18	Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, Chen H, Omeroglu G, Meterissian S, Omeroglu A, et al: Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 14:518–527. 2008. View Article : Google Scholar : PubMed/NCBI
19	Crabtree JS, Jelinsky SA, Harris HA, Choe SE, Cotreau MM, Kimberland ML, Wilson E, Saraf KA, Liu W, McCampbell AS, et al: Comparison of human and rat uterine leiomyomata: Identification of a dysregulated mammalian target of rapamycin pathway. Cancer Res. 69:6171–6178. 2009. View Article : Google Scholar : PubMed/NCBI
20	Hao Y, Triadafilopoulos G, Sahbaie P, Young HS, Omary MB and Lowe AW: Gene expression profiling reveals stromal genes expressed in common between Barrett's esophagus and adenocarcinoma. Gastroenterology. 131:925–933. 2006. View Article : Google Scholar : PubMed/NCBI
21	Szatkowski C, Parys JB, Ouadid-Ahidouch H and Matifat F: Research Inositol 1,4,5-trisphosphate-induced Ca2+ signalling is involved in estradiol-induced breast cancer epithelial cell growth. Mol Cancer. 9:1562010. View Article : Google Scholar : PubMed/NCBI
22	Mariot P, Prevarskaya N, Roudbaraki MM, Le Bourhis X, Van Coppenolle F, Vanoverberghe K and Skryma R: Evidence of functional ryanodine receptor involved in apoptosis of prostate cancer (LNCaP) cells. Prostate. 43:205–214. 2000. View Article : Google Scholar : PubMed/NCBI
23	Galione A, Evans AM, Ma J, Parrington J, Arredouani A, Cheng X and Zhu MX: The acid test: The discovery of two-pore channels (TPCs) as NAADP-gated endolysosomal Ca(2+) release channels. Pflugers Arch. 458:869–876. 2009. View Article : Google Scholar : PubMed/NCBI
24	Lipkin M and Newmark H: Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 313:1381–1384. 1985. View Article : Google Scholar : PubMed/NCBI
25	Jin T, Zhang Z, Yang XF and Luo JS: S100A4 expression is closely linked to genesis and progression of glioma by regulating proliferation, apoptosis, migration and invasion. Asian Pac J Cancer Prev. 16:2883–2887. 2015. View Article : Google Scholar : PubMed/NCBI
26	Berridge MJ, Bootman MD and Roderick HL: Calcium signalling: Dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 4:517–529. 2003. View Article : Google Scholar : PubMed/NCBI
27	Takeshige N, Yin G, Ohnaka K, Kono S, Ueki T, Tanaka M, Maehara Y, Okamura T, Ikejiri K, Maekawa T, et al: Associations between vitamin D receptor (VDR) gene polymorphisms and colorectal cancer risk and effect modifications of dietary calcium and vitamin D in a Japanese population. Asian Pac J Cancer Prev. 16:2019–2026. 2015. View Article : Google Scholar : PubMed/NCBI
28	Panner A and Wurster RD: T-type calcium channels and tumor proliferation. Cell Calcium. 40:253–259. 2006. View Article : Google Scholar : PubMed/NCBI
29	Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI
30	Linja MJ, Savinainen KJ, Saramäki OR, Tammela TL, Vessella RL and Visakorpi T: Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 61:3550–3555. 2001.PubMed/NCBI
31	Gillett C, Fantl V, Smith R, Fisher C, Bartek J, Dickson C, Barnes D and Peters G: Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining. Cancer Res. 54:1812–1817. 1994.PubMed/NCBI
32	Cole S, Bhardwaj G, Gerlach J, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM and Deeley RG: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science. 258:1650–1654. 1992. View Article : Google Scholar : PubMed/NCBI
33	Liu TH, Guo K, Liu RQ, Zhang S, Huang ZH and Liu YK: The high expressed serum soluble neural cell adhesion molecule, a high risk factor indicating hepatic encephalopathy in hepatocelular carcinoma patients. Asian Pac J Cancer Prev. 16:3131–3135. 2015. View Article : Google Scholar : PubMed/NCBI
34	Mao YY, Jing FY, Jin MJ, Li YJ, Ding Y, Guo J, Wang FJ, Jiang LF and Chen K: rs12904 polymorphism in the 3′UTR of EFNA1 is associated with colorectal cancer susceptibility in a Chinese population. Asian Pac J Cancer Prev. 14:5037–5041. 2013. View Article : Google Scholar : PubMed/NCBI
35	Martino-Echarri E, Fernández-Rodríguez R, Rodríguez-Baena FJ, Barrientos-Durán A, Torres-Collado AX, Plaza-Calonge Mdel C, Amador-Cubero S, Cortés J, Reynolds LE, Hodivala-Dilke KM and Rodríguez-Manzaneque JC: Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen-1 and nidogen-2. Int J Cancer Cancer Cancer. 133:2315–2324. 2013. View Article : Google Scholar
36	Li YP, Tian FG, Shi PC, Guo LY, Wu HM, Chen RQ and Xue JM: 4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization. Asian Pac J Cancer Prev. 15:10151–10156. 2014. View Article : Google Scholar : PubMed/NCBI
37	Kim HS, Patel K, Muldoon-Jacobs K, Bisht KS, Aykin-Burns N, Pennington JD, van der Meer R, Nguyen P, Savage J, Owens KM, et al: SIRT3 is a mitochondria-localized tumor suppressor required for maintenance of mitochondrial integrity and metabolism during stress. Cancer Cell. 17:41–52. 2010. View Article : Google Scholar : PubMed/NCBI
38	Dziegielewska B, Gray LS and Dziegielewski J: T-type calcium channels blockers as new tools in cancer therapies. Pflugers Arch. 466:801–810. 2014. View Article : Google Scholar : PubMed/NCBI
39	Lee JY, Park SJ, Park SJ, Lee MJ, Rhim H, Seo SH and Kim KS: Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers. Bioorg Med Chem Lett. 16:5014–5017. 2006. View Article : Google Scholar : PubMed/NCBI
40	Bertolesi GE, Shi CJ, Elbaum L, Jollimore C, Rozenberg G, Barnes S and Kelly ME: The Ca(2+) channel antagonists mibefradil and pimozide inhibit cell growth via different cytotoxic mechanisms. Mol Pharmacol. 62:210–219. 2002. View Article : Google Scholar : PubMed/NCBI
41	Toyota M, Ho C, Ohe-Toyota M, Baylin SB and Issa JP: Inactivation of CACNA1G, a T-type calcium channel gene, by aberrant methylation of its 5′ CpG island in human tumors. Cancer Res. 59:4535–4541. 1999.PubMed/NCBI
42	Díaz-Lezama N, Hernández-Elvira M, Sandoval A, Monroy A, Felix R and Monjaraz E: Ghrelin inhibits proliferation and increases T-type Ca2+ channel expression in PC-3 human prostate carcinoma cells. Biochem Biophys Res Commun. 403:24–29. 2010. View Article : Google Scholar : PubMed/NCBI
43	Wang CY, Lai MD, Phan NN, Sun ZD and Lin YC: Meta-analysis of public microarray datasets reveals voltage-gated calcium gene signatures in clinical cancer patients. PLoS One. 10:e01257662015. View Article : Google Scholar : PubMed/NCBI
44	Rhodes DR and Chinnaiyan AM: Integrative analysis of the cancer transcriptome. Nat Genet. 37 Suppl:S31–S37. 2005. View Article : Google Scholar : PubMed/NCBI
45	Zhou C, Ren Y, Wang K, Liu J, He JJ and Liu PJ: Intra-operative rectal washout with saline solution can effectively prevent anastomotic recurrence: A meta-analysis. Asian Pac J Cancer Prev. 14:7155–7159. 2013. View Article : Google Scholar : PubMed/NCBI
46	Alqumber MA, Dar SA, Haque S, Wahid M, Singh R and Akhter N: No association of the TGF-β1 29T/C polymorphism with breast cancer risk in caucasian and Asian populations: Evidence from a meta-analysis involving 55, 841 subjects. Asian Pac J Cancer Prev. 15:8725–8734. 2014. View Article : Google Scholar : PubMed/NCBI
47	Ni M, Chen Y, Lim E, Wimberly H, Bailey ST, Imai Y, Rimm DL, Liu XS and Brown M: Targeting androgen receptor in estrogen receptor-negative breast cancer. Cancer Cell. 20:119–131. 2011. View Article : Google Scholar : PubMed/NCBI
48	D'Ambrogio A, Nagaoka K and Richter JD: Translational control of cell growth and malignancy by the CPEBs. Nat Rev Cancer. 13:283–290. 2013. View Article : Google Scholar : PubMed/NCBI
49	Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA, Kim S, Wilson CJ, Lehár J, Kryukov GV, Sonkin D, et al: The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 483:603–607. 2012. View Article : Google Scholar : PubMed/NCBI
50	Ertel EA, Campbell KP, Harpold MM, Hofmann F, Mori Y, Perez-Reyes E, Schwartz A, Snutch TP, Tanabe T, Birnbaumer L, et al: Nomenclature of voltage-gated calcium channels. Neuron. 25:533–535. 2000. View Article : Google Scholar : PubMed/NCBI
51	Cain SM and Snutch TP: Voltage-gated calcium channels and disease. Biofactors. 37:197–205. 2011. View Article : Google Scholar : PubMed/NCBI
52	Bidaud I, Mezghrani A, Swayne LA, Monteil A and Lory P: Voltage-gated calcium channels in genetic diseases. Biochim Biophys Acta. 1763:1169–1174. 2006. View Article : Google Scholar : PubMed/NCBI
53	Kavianpour M, Ahmadzadeh A, Shahrabi S and Saki N: Significance of oncogenes and tumor suppressor genes in AML prognosis. Tumour Biol. 37:10041–10052. 2016. View Article : Google Scholar : PubMed/NCBI
54	Cooper GM and Hausman RE: The cell. Sinauer Associates Sunderland; 2000, PubMed/NCBI
55	Sanchez-Carbayo M, Socci ND, Lozano J, Saint F and Cordon-Cardo C: Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol. 24:778–789. 2006. View Article : Google Scholar : PubMed/NCBI
56	Marta SC, Nicholas S, Juanjo L, Fabien S and Carlos CC: Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. Tumor Biol. 27:47. 2006.
57	Schaldemose EL, Horjales-Araujo E, Demontis D, Børglum AD, Svensson P and Finnerup NB: No association of polymorphisms in the serotonin transporter gene with thermal pain sensation in healthy individuals. Mol Pain. 10:762014. View Article : Google Scholar : PubMed/NCBI
58	Stunnenberg BC, Deinum J, Links TP, Wilde AA, Franssen H and Drost G: Cardiac arrhythmias in hypokalemic periodic paralysis: Hypokalemia as only cause? Muscle Nerve. 50:327–332. 2014. View Article : Google Scholar : PubMed/NCBI
59	Beitelshees AL, Navare H, Wang D, Gong Y, Wessel J, Moss JI, Langaee TY, Cooper-DeHoff RM, Sadee W, Pepine CJ, et al: CACNA1C gene polymorphisms, cardiovascular disease outcomes, and treatment response. Circ Cardiovasc Genet. 2:362–370. 2009. View Article : Google Scholar : PubMed/NCBI
60	Baig SM, Koschak A, Lieb A, Gebhart M, Dafinger C, Nürnberg G, Ali A, Ahmad I, Sinnegger-Brauns MJ, Brandt N, et al: Loss of Cav1. 3 (CACNA1D) function in a human channelopathy with bradycardia and congenital deafness. Nat Neurosci. 14:77–84. 2011. View Article : Google Scholar : PubMed/NCBI
61	Johnson AD, Newton-Cheh C, Chasman DI, Ehret GB, Johnson T, Rose L, Rice K, Verwoert GC, Launer LJ, Gudnason V, et al: Association of hypertension drug target genes with blood pressure and hypertension in 86 588 individuals. Hypertension. 57:903–910. 2011. View Article : Google Scholar : PubMed/NCBI
62	Madden E: Differential gene remodeling in overweight and obese patients with heart failure. 2013.
63	Kang H, Yang X, Chen R, Zhang B, Corona E, Schadt EE and Butte AJ: Integration of disease-specific single nucleotide polymorphisms, expression quantitative trait loci and coexpression networks reveal novel candidate genes for type 2 diabetes. Diabetologia. 55:2205–2213. 2012. View Article : Google Scholar : PubMed/NCBI
64	Reinbothe TM, Alkayyali S, Ahlqvist E, Tuomi T, Isomaa B, Lyssenko V and Renström E: The human L-type calcium channel Cav1. 3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes. Diabetologia. 56:340–349. 2013.
65	Reinbothe T, Lyssenko V, Lang S and Renström E: Polymorphisms in CACNA1D affect insulin release and channel expression and associate with type 2 diabetes46th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD). Springer; pp. 2962010;
66	Qiu ZX, Zhao S, Li L and Li WM: Loss of expression of PTEN is associated with worse prognosis in patients with cancer. Asian Pac J Cancer Prev. 16:4691–4698. 2015. View Article : Google Scholar : PubMed/NCBI
67	Kamp TJ and Hell JW: Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Cir Res. 87:1095–1102. 2000. View Article : Google Scholar
68	Moosmang S, Schulla V, Welling A, Feil R, Feil S, Wegener JW, Hofmann F and Klugbauer N: Dominant role of smooth muscle L-type calcium channel Cav1. 2 for blood pressure regulation. EMBO J. 22:6027–6034. 2003. View Article : Google Scholar : PubMed/NCBI
69	Bhat S, Dao DT, Terrillion CE, Arad M, Smith RJ, Soldatov NM and Gould TD: CACNA1C (Ca v 1.2) in the pathophysiology of psychiatric disease. Prog Neurobiol. 99:1–14. 2012. View Article : Google Scholar : PubMed/NCBI
70	Sun L, Hui AM, Su Q, Vortmeyer A, Kotliarov Y, Pastorino S, Passaniti A, Menon J, Walling J, Bailey R, et al: Neuronal and glioma-derived stem cell factor induces angiogenesis within the brain. Cancer Cell. 9:287–300. 2006. View Article : Google Scholar : PubMed/NCBI
71	Murat A, Migliavacca E, Gorlia T, Lambiv WL, Shay T, Hamou MF, de Tribolet N, Regli L, Wick W, Kouwenhoven MC, et al: Stem cell-related ‘self-renewal’ signature and high epidermal growth factor receptor expression associated with resistance to concomitant chemoradiotherapy in glioblastoma. J Clin Oncol. 26:3015–3024. 2008. View Article : Google Scholar : PubMed/NCBI
72	Uchitel OD, Protti DA, Sanchez V, Cherksey BD, Sugimori M and Llinás R: P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc Natl Acad Sci USA. 89:pp. 3330–3333. 1992; View Article : Google Scholar : PubMed/NCBI
73	Catterall WA: Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. Cell Calcium. 24:307–323. 1998. View Article : Google Scholar : PubMed/NCBI
74	Piccaluga PP, Agostinelli C, Califano A, Rossi M, Basso K, Zupo S, Went P, Klein U, Zinzani PL, Baccarani M, et al: Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. J Clin Invest. 117:823–834. 2007. View Article : Google Scholar : PubMed/NCBI
75	Gazulla J and Tintore M: P/Q-type voltage-dependent calcium channels in neurological disease. Neurologia. 22:511–516. 2007.(In Spanish). PubMed/NCBI
76	Jensen RL, Petr M and Wurster RD: Calcium channel antagonist effect on in vitro meningioma signal transduction pathways after growth factor stimulation. Neurosurgery. 46:692–703. 2000. View Article : Google Scholar : PubMed/NCBI
77	Lee YS, Sayeed MM and Wurster RD: Inhibition of cell growth and intracellular Ca2+ mobilization in human brain tumor cells by Ca2+ channel antagonists. Mol Chem Neuropathol. 22:81–95. 1994. View Article : Google Scholar : PubMed/NCBI
78	Jensen RL, Origitano TC, Lee YS, Weber M and Wurster RD: In vitro growth inhibition of growth factor-stimulated meningioma cells by calcium channel antagonists. Neurosurgery. 36:365–374. 1995. View Article : Google Scholar : PubMed/NCBI
79	Latour I, Louw DF, Beedle AM, Hamid J, Sutherland GR and Zamponi GW: Expression of T-type calcium channel splice variants in human glioma. Glia. 48:112–119. 2004. View Article : Google Scholar : PubMed/NCBI
80	Schorge S and Rajakulendran S: The P/Q channel in human disease: untangling the genetics and physiology. WIREs Membr Transp Signal. 1:311–320. 2012. View Article : Google Scholar
81	Ophoff RA, Terwindt GM, Vergouwe MN, van Eijk R, Oefner PJ, Hoffman SM, Lamerdin JE, Mohrenweiser HW, Bulman DE, Ferrari M, et al: Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell. 87:543–552. 1996. View Article : Google Scholar : PubMed/NCBI
82	Zhuchenko O, Bailey J, Bonnen P, Ashizawa T, Stockton DW, Amos C, Dobyns WB, Subramony SH, Zoghbi HY, Lee CC, et al: Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha1A-voltage-dependent calcium channel. Nat Genet. 15:62–69. 1997. View Article : Google Scholar : PubMed/NCBI
83	Bürk K, Kaiser FJ, Tennstedt S, Schöls L, Kreuz FR, Wieland T, Strom TM, Büttner T, Hollstein R, Braunholz D, et al: A novel missense mutation in CACNA1A evaluated by in silico protein modeling is associated with non-episodic spinocerebellar ataxia with slow progression. Eur J Med Genet. 57:207–211. 2014. View Article : Google Scholar : PubMed/NCBI
84	Sintas C, Carreño O, Corominas R, Serra SA, Vila M, Fernández-Castillo N, Toma C, Pons R, Llaneza M, Sobrido MJ, et al: Screening of cacna1a and ATP1A2 genes in hemiplegic migraine: Clinical, genetic and functional studies. J Headache Pain. 14 Suppl 1:P262013. View Article : Google Scholar
85	Verschuur-Maes AH, de Bruin PC and van Diest PJ: Epigenetic progression of columnar cell lesions of the breast to invasive breast cancer. Breast Cancer Res Treat. 136:705–715. 2012. View Article : Google Scholar : PubMed/NCBI
86	Castro M, Grau L, Puerta P, Gimenez L, Venditti J, Quadrelli S and Sánchez-Carbayo M: Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer. J Transl Med. 8:862010. View Article : Google Scholar : PubMed/NCBI
87	Burger PC, Yu I, Tihan T, et al: Atypical teratoid/rhabdoid tumor of the central nervous system: A highly malignant tumor of infancy and childhood frequently mistaken for medulloblastoma: A pediatric oncology group study. Am J Surg Pathol. 22:1083–1092. 1998. View Article : Google Scholar : PubMed/NCBI
88	Roderick HL and Cook SJ: Ca2+ signalling checkpoints in cancer: Remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer. 8:361–375. 2008. View Article : Google Scholar : PubMed/NCBI
89	Tomlins SA, Laxman B, Varambally S, Cao X, Yu J, Helgeson BE, Cao Q, Prensner JR, Rubin MA, Shah RB, et al: Role of the TMPRSS2-ERG gene fusion in prostate cancer. Neoplasia. 10:177–188. 2008. View Article : Google Scholar : PubMed/NCBI
90	Chen R, Zeng X, Zhang R, Huang J, Kuang X, Yang J, Liu J, Tawfik O, Thrasher JB and Li B: Cav1.3 channel α1D protein is overexpressed and modulates androgen receptor transactivation in prostate cancers. Urol Oncol. 32:524–536. 2014. View Article : Google Scholar : PubMed/NCBI
91	Liu Z, Christudass C, Zhang H, et al: A novel quantitative histomorphological tool to assess multiple biomarkers to predict prostate cancer aggression. Cancer Res. 74 19 Suppl:S40132014. View Article : Google Scholar
92	Ricci M, Xu Y, Hammond HL, Willoughby DA, Nathanson L, Rodriguez MM, Vatta M, Lipshultz SE and Lincoln J: Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome. PLoS One. 7:e297842012. View Article : Google Scholar : PubMed/NCBI
93	Dutton Regester K and Hayward NK: Reviewing the somatic genetics of melanoma: From current to future analytical approaches. Pigment Cell Melanoma Res. 25:144–154. 2012. View Article : Google Scholar : PubMed/NCBI
94	Jones J, Otu H, Spentzos D, Kolia S, Inan M, Beecken WD, Fellbaum C, Gu X, Joseph M, Pantuck AJ, et al: Gene signatures of progression and metastasis in renal cell cancer. Clin Cancer Res. 11:5730–5739. 2005. View Article : Google Scholar : PubMed/NCBI
95	Ginos MA, Page GP, Michalowicz BS, Patel KJ, Volker SE, Pambuccian SE, Ondrey FG, Adams GL and Gaffney PM: Identification of a gene expression signature associated with recurrent disease in squamous cell carcinoma of the head and neck. Cancer Res. 64:55–63. 2004. View Article : Google Scholar : PubMed/NCBI
96	Estilo CL, O-charoenrat P, Talbot S, Socci ND, Carlson DL, Ghossein R, Williams T, Yonekawa Y, Ramanathan Y, Boyle JO, et al: Oral tongue cancer gene expression profiling: Identification of novel potential prognosticators by oligonucleotide microarray analysis. BMC Cancer. 9:112009. View Article : Google Scholar : PubMed/NCBI
97	Talbot SG, Estilo C, Maghami E, Sarkaria IS, Pham DK, O-charoenrat P, Socci ND, Ngai I, Carlson D, Ghossein R, et al: Gene expression profiling allows distinction between primary and metastatic squamous cell carcinomas in the lung. Cancer Res. 65:3063–3071. 2005.PubMed/NCBI
98	Basso K, Margolin AA, Stolovitzky G, Klein U, Dalla-Favera R and Califano A: Reverse engineering of regulatory networks in human B cells. Nat Genet. 37:382–390. 2005. View Article : Google Scholar : PubMed/NCBI
99	Yoshihara K, Tajima A, Komata D, et al: Gene expression profiling of advanced-stage serous ovarian cancers distinguishes novel subclasses and implicates ZEB2 in tumor progression and prognosis. Cancer Sci. 100:1421–1428. 2009. View Article : Google Scholar : PubMed/NCBI
100	Sanchez-Carbayo M, Socci ND, Lozano J, Saint F and Cordon-Cardo C: Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays. J Clin Oncol. 24:778–789. 2006. View Article : Google Scholar : PubMed/NCBI
101	Tomlins SA, Mehra R, Rhodes DR, et al: Integrative molecular concept modeling of prostate cancer progression. Nat Genet. 39:41–51. 2007. View Article : Google Scholar : PubMed/NCBI
102	Yusenko MV, Kuiper RP, Boethe T, Ljungberg B, van Kessel AG and Kovacs G: High-resolution DNA copy number and gene expression analyses distinguish chromophobe renal cell carcinomas and renal oncocytomas. BMC Cancer. 9:1522009. View Article : Google Scholar : PubMed/NCBI
103	Frierson HF Jr, El-Naggar AK, Welsh JB, Sapinoso LM, Su AI, Cheng J, Saku T, Moskaluk CA and Hampton GM: Large scale molecular analysis identifies genes with altered expression in salivary adenoid cystic carcinoma. Am J Pathol. 161:1315–1323. 2002. View Article : Google Scholar : PubMed/NCBI
104	Biewenga P, Buist MR, Moerland PD, Ver Loren van Themaat E, van Kampen AH, ten Kate FJ and Baas F: Gene expression in early stage cervical cancer. Gynecol Oncol. 108:520–526. 2008. View Article : Google Scholar : PubMed/NCBI
105	Hou J, Aerts J, den Hamer B, van Ijcken W, den Bakker M, Riegman P, van der Leest C, van der Spek P, Foekens JA, Hoogsteden HC, et al: Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One. 5:e103122010. View Article : Google Scholar : PubMed/NCBI
106	Okayama H, Kohno T, Ishii Y, Shimada Y, Shiraishi K, Iwakawa R, Furuta K, Tsuta K, Shibata T, Yamamoto S, et al: Identification of genes upregulated in ALK-positive and EGFR/KRAS/ALK-negative lung adenocarcinomas. Cancer Res. 72:100–111. 2012. View Article : Google Scholar : PubMed/NCBI
107	Wurmbach E, Chen YB, Khitrov G, Zhang W, Roayaie S, Schwartz M, Fiel I, Thung S, Mazzaferro V, Bruix J, et al: Genome-wide molecular profiles of HCV-induced dysplasia and hepatocellular carcinoma. Hepatology. 45:938–947. 2007. View Article : Google Scholar : PubMed/NCBI
108	Detwiller KY, Fernando NT, Segal NH, Ryeom SW, D'Amore PA and Yoon SS: Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A. Cancer Res. 65:5881–5889. 2005. View Article : Google Scholar : PubMed/NCBI
109	Rickman DS, Bobek MP, Misek DE, Kuick R, Blaivas M, Kurnit DM, Taylor J and Hanash SM: Distinctive molecular profiles of high-grade and low-grade gliomas based on oligonucleotide microarray analysis. Cancer Res. 61:6885–6891. 2001.PubMed/NCBI
110	Shai R, Shi T, Kremen TJ, Horvath S, Liau LM, Cloughesy TF, Mischel PS and Nelson SF: Gene expression profiling identifies molecular subtypes of gliomas. Oncogene. 22:4918–4923. 2003. View Article : Google Scholar : PubMed/NCBI
111	Hong Y, Downey T, Eu KW, Koh PK and Cheah PY: A ‘metastasis-prone’ signature for early-stage mismatch-repair proficient sporadic colorectal cancer patients and its implications for possible therapeutics. Clin Exp Metastasis. 27:83–90. 2010. View Article : Google Scholar : PubMed/NCBI
112	Sabates-Bellver J, van der Flier LG, de Palo M, et al: Transcriptome profile of human colorectal adenomas. Mol Cancer Res. 5:1263–1275. 2007. View Article : Google Scholar : PubMed/NCBI
113	D'Errico M, de Rinaldis E, Blasi MF, Viti V, Falchetti M, Calcagnile A, Sera F, Saieva C, Ottini L, Palli D, et al: Genome-wide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer. 45:461–469. 2009. View Article : Google Scholar
114	Turashvili G, Bouchal J, Baumforth K, Wei W, Dziechciarkova M, Ehrmann J, Klein J, Fridman E, Skarda J, Srovnal J, et al: Novel markers for differentiation of lobular and ductal invasive breast carcinomas by laser microdissection and microarray analysis. BMC Cancer. 7:552007. View Article : Google Scholar : PubMed/NCBI
115	Lee J, Kotliarova S, Kotliarov Y, Li A, Su Q, Donin NM, Pastorino S, Purow BW, Christopher N, Zhang W, et al: Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 9:391–403. 2006. View Article : Google Scholar : PubMed/NCBI
116	Lee JS, Leem SH, Lee SY, Kim SC, Park ES, Kim SB, Kim SK, Kim YJ, Kim WJ and Chu IS: Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors. J Clin Oncol. 28:2660–2667. 2010. View Article : Google Scholar : PubMed/NCBI
117	Bhattacharjee A, Richards WG, Staunton J, Li C, Monti S, Vasa P, Ladd C, Beheshti J, Bueno R, Gillette M, et al: Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA. 98:pp. 13790–13795. 2001; View Article : Google Scholar : PubMed/NCBI
118	Gluck S, Ross JS, Royce M, McKenna EF Jr, Perou CM, Avisar E and Wu L: TP53 genomics predict higher clinical and pathologic tumor response in operable early-stage breast cancer treated with docetaxel-capecitabine ± trastuzumab. Breast Cancer Res Treat. 132:781–791. 2012. View Article : Google Scholar : PubMed/NCBI
119	French PJ, Swagemakers SM, Nagel JH, Kouwenhoven MC, Brouwer E, van der Spek P, Luider TM, Kros JM, van den Bent MJ and Smitt PA Sillevis: Gene expression profiles associated with treatment response in oligodendrogliomas. Cancer Res. 65:11335–11344. 2005. View Article : Google Scholar : PubMed/NCBI
120	Wang Q, Wen YG, Li DP, Xia J, Zhou CZ, Yan DW, Tang HM and Peng ZH: Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol. 29:77–83. 2012. View Article : Google Scholar : PubMed/NCBI
121	Haslinger C, Schweifer N, Stilgenbauer S, Döhner H, Lichter P, Kraut N, Stratowa C and Abseher R: Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status. J Clin Oncol. 22:3937–3949. 2004. View Article : Google Scholar : PubMed/NCBI