Tumor suppressor genes associated with drug resistance in ovarian cancer (Review)

Yin,Fuqiang; Liu,Xia; Li,Danrong; Wang,Qi; Zhang,Wei; Li,Li

doi:10.3892/or.2013.2446

Tumor suppressor genes associated with drug resistance in ovarian cancer (Review)

Authors:
- Fuqiang Yin
- Xia Liu
- Danrong Li
- Qi Wang
- Wei Zhang
- Li Li
View Affiliations

Affiliations: Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi 530021, P.R. China, Center for Translational Medicine, Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
Published online on: May 9, 2013 https://doi.org/10.3892/or.2013.2446
Pages: 3-10

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

Ovarian cancer is a fatal gynecological cancer and a major cause of cancer-related mortality worldwide. The main limitation to a successful treatment for ovarian cancer is the development of drug resistance to combined chemotherapy. Tumor suppressor genes (TSGs) are wild-type alleles of genes which play regulatory roles in diverse cellular activities, and whose loss of function contributes to the development of cancer. It has been demonstrated that TSGs contribute to drug resistance in several types of solid tumors. However, an overview of the contribution of TSGs to drug resistance in ovarian cancer has not previously been reported. In this study, 15 TSGs responding to drug resistance in ovarian cancer were reviewed to determine the relationship of TSGs with ovarian cancer drug resistance. Furthermore, gene/protein-interaction and bio-association analysis were performed to demonstrate the associations of these TSGs and to mine the potential drug resistance-related genes in ovarian cancer. We observed that the 15 TSGs had close interactions with each other, suggesting that they may contribute to drug resistance in ovarian cancer as a group. Five pathways/processes consisting of DNA damage, apoptosis, cell cycle, DNA binding and methylation may be the key ways with which TSGs participate in the regulation of drug resistance. In addition, ubiquitin C (UBC) and six additional TSGs including the adenomatous polyposis coli gene (APC), death associated protein kinase gene (DAPK), pleiomorphic adenoma gene-like 1 (PLAGL1), retinoblastoma susceptibility gene (RB1), a gene encoding an apoptosis-associated speck-like protein (PYCARD/ASC) and tumor protein 63 (TP63), which had close interactions with the 15 TSGs, are potential drug resistance-related genes in ovarian cancer.

View Figures

View References

1	Balch C, Huang TH, Brown R and Nephew KP: The epigenetics of ovarian cancer drug resistance and resensitization. Am J Obstet Gynecol. 191:1552–1572. 2004. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar
3	Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G and Ferlini C: Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol. 111:478–486. 2008. View Article : Google Scholar : PubMed/NCBI
4	Gottesman MM: Mechanisms of cancer drug resistance. Annu Rev Med. 53:615–627. 2002. View Article : Google Scholar : PubMed/NCBI
5	Johnson SW, Ozols RF and Hamilton TC: Mechanisms of drug resistance in ovarian cancer. Cancer. 71(Suppl 2): S644–S649. 1993. View Article : Google Scholar : PubMed/NCBI
6	Fraser M, Leung BM, Yan X, Dan HC, Cheng JQ and Tsang BK: p53 is a determinant of X-linked inhibitor of apoptosis protein/Akt-mediated chemoresistance in human ovarian cancer cells. Cancer Res. 63:7081–7088. 2003.PubMed/NCBI
7	Cheng JQ, Jiang X, Fraser M, Li M, Dan HC, Sun M and Tsang BK: Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway. Drug Resist Updat. 5:131–146. 2002. View Article : Google Scholar : PubMed/NCBI
8	Sager R: Tumor suppressor genes: the puzzle and the promise. Science. 246:1406–1412. 1989. View Article : Google Scholar : PubMed/NCBI
9	Sherr CJ: Principles of tumor suppression. Cell. 116:235–246. 2004. View Article : Google Scholar : PubMed/NCBI
10	Shanker M, Jin J, Branch CD, Miyamoto S, Grimm EA, Roth JA and Ramesh R: Tumor suppressor gene-based nanotherapy: from test tube to the clinic. J Drug Deliv. 2011:4658452011. View Article : Google Scholar : PubMed/NCBI
11	Kaur M, Radovanovic A, Essack M, et al: Database for exploration of functional context of genes implicated in ovarian cancer. Nucleic Acids Res. 37:D820–D823. 2009. View Article : Google Scholar : PubMed/NCBI
12	Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 474:609–615. 2011. View Article : Google Scholar
13	Bast RC Jr, Hennessy B and Mills GB: The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 9:415–428. 2009. View Article : Google Scholar : PubMed/NCBI
14	Zhao M, Sun J and Zhao Z: Distinct and competitive regulatory patterns of tumor suppressor genes and oncogenes in ovarian cancer. PLoS One. 7:e441752012. View Article : Google Scholar : PubMed/NCBI
15	Chen H, Hardy TM and Tollefsbol TO: Epigenomics of ovarian cancer and its chemoprevention. Front Genet. 2:672011. View Article : Google Scholar : PubMed/NCBI
16	Matei D, Shen C, Fang F, et al: A phase II study of decitabine and carboplatin in recurrent platinum (Pt)-resistant ovarian cancer (OC). J Clin Oncol. 29(Suppl): abst 5011. 2011.
17	Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK and Zhang W: Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA. 306:1557–1565. 2011. View Article : Google Scholar : PubMed/NCBI
18	Zhou C, Smith JL and Liu J: Role of BRCA1 in cellular resistance to paclitaxel and ionizing radiation in an ovarian cancer cell line carrying a defective BRCA1. Oncogene. 22:2396–2404. 2003. View Article : Google Scholar : PubMed/NCBI
19	Borst P, Rottenberg S and Jonkers J: How do real tumors become resistant to cisplatin? Cell Cycle. 7:1353–1359. 2008. View Article : Google Scholar : PubMed/NCBI
20	Wang Y, Wiltshire T, Senft J, Reed E and Wang W: Irofulven induces replication-dependent CHK2 activation related to p53 status. Biochem Pharmacol. 73:469–480. 2007. View Article : Google Scholar : PubMed/NCBI
21	Zhang P, Gao W, Li H, Reed E and Chen F: Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells. Biochem Biophys Res Commun. 328:567–572. 2005. View Article : Google Scholar : PubMed/NCBI
22	Chou JL, Su HY, Chen LY, et al: Promoter hypermethylation of FBXO32, a novel TGF-beta/SMAD4 target gene and tumor suppressor, is associated with poor prognosis in human ovarian cancer. Lab Invest. 90:414–425. 2010. View Article : Google Scholar : PubMed/NCBI
23	Plumb JA, Strathdee G, Sludden J, Kaye SB and Brown R: Reversal of drug resistance in human tumor xenografts by 2′-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. Cancer Res. 60:6039–6044. 2000.
24	Strathdee G, MacKean MJ, Illand M and Brown R: A role for methylation of the hMLH1 promoter in loss of hMLH1 expression and drug resistance in ovarian cancer. Oncogene. 18:2335–2341. 1999. View Article : Google Scholar : PubMed/NCBI
25	Staub J, Chien J, Pan Y, et al: Epigenetic silencing of HSulf-1 in ovarian cancer: implications in chemoresistance. Oncogene. 26:4969–4978. 2007. View Article : Google Scholar : PubMed/NCBI
26	Liu P, Gou M, Yi T, et al: Efficient inhibition of an intraperitoneal xenograft model of human ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin-polyethyleneimine nanogels. Oncol Rep. 27:363–370. 2012.
27	Gopalan B, Shanker M, Scott A, Branch CD, Chada S and Ramesh R: MDA-7/IL-24, a novel tumor suppressor/cytokine is ubiquitinated and regulated by the ubiquitin-proteasome system, and inhibition of MDA-7/IL-24 degradation enhances the antitumor activity. Cancer Gene Ther. 15:1–8. 2008. View Article : Google Scholar
28	Xiong J, Peng ZL and Tan X: Effects of adenoviral-mediated mda-7/IL-24 gene infection on the growth and drug-resistance of drug-resistant. Sichuan Da Xue Xue Bao Yi Xue Ban. 38:433–436. 2007.(In Chinese).
29	Kawakami Y, Hama S, Hiura M, et al: Adenovirus-mediated p16 gene transfer changes the sensitivity to taxanes and Vinca alkaloids of human ovarian cancer cells. Anticancer Res. 21:2537–2545. 2001.PubMed/NCBI
30	Takai N and Narahara H: Histone deacetylase inhibitor therapy in epithelial ovarian cancer. J Oncol. 2010:4584312010. View Article : Google Scholar : PubMed/NCBI
31	Xia X, Ma Q, Li X, et al: Cytoplasmic p21 is a potential predictor for cisplatin sensitivity in ovarian cancer. BMC Cancer. 11:3992011. View Article : Google Scholar : PubMed/NCBI
32	Materna V, Surowiak P, Markwitz E, Spaczynski M, Drag-Zalesinska M, Zabel M and Lage H: Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients. Oncol Rep. 17:505–516. 2007.PubMed/NCBI
33	Cao Z, Yoon JH, Nam SW, Lee JY and Park WS: PDCD4 expression inversely correlated with miR-21 levels in gastric cancers. J Cancer Res Clin Oncol. 138:611–619. 2012. View Article : Google Scholar : PubMed/NCBI
34	Zhang X, Wang X, Song X, et al: Programmed cell death 4 enhances chemosensitivity of ovarian cancer cells by activating death receptor pathway in vitro and in vivo. Cancer Sci. 101:2163–2170. 2010. View Article : Google Scholar : PubMed/NCBI
35	Yang H, Kong W, He L, et al: MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN. Cancer Res. 68:425–433. 2008. View Article : Google Scholar : PubMed/NCBI
36	Lee S, Choi EJ, Jin C and Kim DH: Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line. Gynecol Oncol. 97:26–34. 2005. View Article : Google Scholar : PubMed/NCBI
37	Wu H, Cao Y, Weng D, et al: Effect of tumor suppressor gene PTEN on the resistance to cisplatin in human ovarian cancer cell lines and related mechanisms. Cancer Lett. 271:260–271. 2008. View Article : Google Scholar : PubMed/NCBI
38	Yan X, Fraser M, Qiu Q and Tsang BK: Over-expression of PTEN sensitizes human ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner. Gynecol Oncol. 102:348–355. 2006. View Article : Google Scholar : PubMed/NCBI
39	Kassler S, Donninger H, Birrer MJ and Clark GJ: RASSF1A and the Taxol response in ovarian cancer. Mol Biol Int. 2012:2632672012. View Article : Google Scholar : PubMed/NCBI
40	Chmelarova M, Krepinska E, Spacek J, Laco J, Beranek M and Palicka V: Methylation in the p53 promoter in epithelial ovarian cancer. Clin Transl Oncol. 15:160–162. 2013. View Article : Google Scholar : PubMed/NCBI
41	Reles A, Wen WH, Schmider A, et al: Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res. 7:2984–2997. 2001.PubMed/NCBI
42	Zhang YL, Guo XR, Shen DH, Cheng YX, Liang XD, Chen YX and Wang Y: Expression and promotor methylation of p73 gene in ovarian epithelial tumors. Zhonghua Bing Li Xue Za Zhi. 41:33–38. 2012.(In Chinese).
43	Al-Bahlani S, Fraser M, Wong AY, Sayan BS, Bergeron R, Melino G and Tsang BK: P73 regulates cisplatin-induced apoptosis in ovarian cancer cells via a calcium/calpain-dependent mechanism. Oncogene. 30:4219–4230. 2011. View Article : Google Scholar : PubMed/NCBI
44	Yang W, Cui S, Ma J, Lu Q, Kong C, Liu T and Sun Z: Cigarette smoking extract causes hypermethylation and inactivation of WWOX gene in T-24 human bladder cancer cells. Neoplasma. 59:216–223. 2012. View Article : Google Scholar : PubMed/NCBI
45	Liu YY, Li L, Li DR, Zhang W and Wang Q: Suppression of WWOX gene by RNA interference reverses platinum resistance acquired in SKOV3/SB cells. Zhonghua Fu Chan Ke Za Zhi. 43:854–858. 2008.(In Chinese).
46	Sharan R, Ulitsky I and Shamir R: Network-based prediction of protein function. Mol Syst Biol. 3:882007. View Article : Google Scholar : PubMed/NCBI
47	Mostafavi S, Ray D, Warde-Farley D, Grouios C and Morris Q: GeneMANIA: a real-time multiple association network integration algorithm for predicting gene function. Genome Biol. 9(Suppl 1): S42008. View Article : Google Scholar : PubMed/NCBI
48	Huang X and Guo B: Adenomatous polyposis coli determines sensitivity to histone deacetylase inhibitor-induced apoptosis in colon cancer cells. Cancer Res. 66:9245–9251. 2006. View Article : Google Scholar
49	Ogawa T, Liggett TE, Melnikov AA, et al: Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance. Cell Cycle. 11:1656–1663. 2012. View Article : Google Scholar : PubMed/NCBI
50	Berge EO, Knappskog S, Geisler S, et al: Identification and characterization of retinoblastoma gene mutations disturbing apoptosis in human breast cancers. Mol Cancer. 9:1732010. View Article : Google Scholar : PubMed/NCBI
51	Ramachandran K, Gordian E and Singal R: 5-azacytidine reverses drug resistance in bladder cancer cells. Anticancer Res. 31:3757–3766. 2011.PubMed/NCBI
52	Ramachandran K, Miller H, Gordian E, Rocha-Lima C and Singal R: Methylation-mediated silencing of TMS1 in pancreatic cancer and its potential contribution to chemosensitivity. Anticancer Res. 30:3919–3925. 2010.PubMed/NCBI
53	Tomkova K, Tomka M and Zajac V: Contribution of p53, p63, and p73 to the developmental diseases and cancer. Neoplasma. 55:177–181. 2008.PubMed/NCBI
54	Lo Nigro C, Monteverde M, Riba M, et al: Expression profiling and long lasting responses to chemotherapy in metastatic gastric cancer. Int J Oncol. 37:1219–1228. 2010.PubMed/NCBI
55	Zhang X, Gu L, Li J, et al: Degradation of MDM2 by the interaction between berberine and DAXX leads to potent apoptosis in MDM2-overexpressing cancer cells. Cancer Res. 70:9895–9904. 2010. View Article : Google Scholar : PubMed/NCBI
56	Poyurovsky MV, Katz C, Laptenko O, et al: The C terminus of p53 binds the N-terminal domain of MDM2. Nat Struct Mol Biol. 17:982–989. 2010. View Article : Google Scholar : PubMed/NCBI
57	Mir R, Tortosa A, Martinez-Soler F, et al: Mdm2 antagonists induce apoptosis and synergize with cisplatin overcoming chemoresistance in TP53 wild-type ovarian cancer cells. Int J Cancer. 132:1525–1536. 2013. View Article : Google Scholar : PubMed/NCBI
58	Kanayama H, Tanaka K, Aki M, et al: Changes in expressions of proteasome and ubiquitin genes in human renal cancer cells. Cancer Res. 51:6677–6685. 1991.PubMed/NCBI
59	Jiang RD, Zhang LX, Yue W, et al: Establishment of a human nasopharyngeal carcinoma drug-resistant cell line CNE2/DDP and screening of drug-resistant genes. Ai Zheng. 22:337–345. 2003.(In Chinese).
60	Jenssen TK, Laegreid A, Komorowski J and Hovig E: A literature network of human genes for high-throughput analysis of gene expression. Nat Genet. 28:21–28. 2001. View Article : Google Scholar : PubMed/NCBI
61	Casorelli I, Bossa C and Bignami M: DNA damage and repair in human cancer: molecular mechanisms and contribution to therapy-related leukemias. Int J Environ Res Public Health. 9:2636–2657. 2012. View Article : Google Scholar : PubMed/NCBI
62	Li J, Feng Q, Kim JM, et al: Human ovarian cancer and cisplatin resistance: possible role of inhibitor of apoptosis proteins. Endocrinology. 142:370–380. 2001.PubMed/NCBI
63	Shah MA and Schwartz GK: Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clin Cancer Res. 7:2168–2181. 2001.PubMed/NCBI