Decreased c-Abl activity in PC-3 and LNCaP prostate cancer cells overexpressing the early growth response-1 protein

Parra,Eduardo; Ferreira,Jorge; Gutierrez,Luis

doi:10.3892/or.2013.2829

Decreased c-Abl activity in PC-3 and LNCaP prostate cancer cells overexpressing the early growth response-1 protein

Authors:
- Eduardo Parra
- Jorge Ferreira
- Luis Gutierrez
View Affiliations

Affiliations: Laboratory of Experimental Biomedicine, University of Tarapaca, Campus Esmeralda, Iquique, Chile, Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, Santiago, Chile, Faculty of Sciences, Arturo Prat University, Iquique, Chile
Published online on: October 31, 2013 https://doi.org/10.3892/or.2013.2829
Pages: 422-427

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

Early growth response-1 (Egr-1) and the non‑receptor protein tyrosine kinase (c-Abl) are 2 response genes that can act as regulators of cell growth and apoptosis in response to stress. Both Egr-1 and c-Abl regulate cell proliferation and survival in different types of cancer cells. To study the effect of overexpression of EGR-1 on the activity of c-Abl in prostate cancer cells, human PC-3 and LNCaP cells were transfected with a control vector or a vector containing the murine Egr-1 cDNA and assessed for the expression of the c-Abl gene. Cells overexpressing Egr-1 were studied with respect to apoptosis (Annexin V)/DEVDase activity, Egr-1/c-Abl activation (western blotting) and cell proliferation (MTT assay). The cells were exposed to tumor necrosis factor α (TNF-α), a known inductor of Egr-1, to c-Abl inhibitor STI-571 and to small interfering RNA (siRNA)-Egr-1, respectively. The results from our studies strongly suggest that overexpression of Egr-1 decreased c-Abl activity independent of endogenous Egr-1 inhibition by siRNA-Egr-1.

View Figures

View References

1	American Cancer Society. Cancer Facts & Figures 2003. American Cancer Society; Atlanta, GA: 2003
2	Quinn M and Babb P: Patterns and trends in prostate cancer incidence, survival, prevalence, and mortality. Part I: international comparisons. BJU Int. 90:162–173. 2002. View Article : Google Scholar : PubMed/NCBI
3	Grönberg H: Prostate cancer epidemiology. Lancet. 361:859–864. 2003.PubMed/NCBI
4	Kaufmann K and Thiel G: Epidermal growth factor and platelet-derived growth factor induce expression of Egr-1, a zinc finger transcription factor, in human malignant glioma cells. J Neurol Sci. 189:83–91. 2001. View Article : Google Scholar : PubMed/NCBI
5	Kaufmann K and Thiel G: Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr-1, a zinc finger transcriptional regulator. J Cell Biochem. 85:381–391. 2002. View Article : Google Scholar
6	Liu C, Rangnekar VM, Adamson E and Mercola D: Suppression of growth and transformation and induction of apoptosis by EGR-1. Cancer Gene Ther. 5:3–28. 1998.PubMed/NCBI
7	Parra E, Ferreira J and Saenz L: Inhibition of Egr-1 by siRNA in prostate carcinoma cell lines is associated with decreased expression of AP-1 and NF-κB. Int J Mol Med. 28:847–853. 2011.PubMed/NCBI
8	Parra E, Ferreira J and Ortega A: Overexpression of EGR-1 modulates the activity of NF-κB and AP-1 in prostate carcinoma PC-3 and LNCaP cell lines. Int J Oncol. 39:345–352. 2011.PubMed/NCBI
9	Parra E, Ortega A and Saenz L: Downregulation of Egr-1 by siRNA inhibits growth of human prostate carcinoma cell line PC-3. Oncol Rep. 22:1513–1518. 2009.PubMed/NCBI
10	Lee CG, Cho SJ, Kang MJ, Chapoval SP, Lee PJ, Noble PW, Yehualaeshet T, Lu B, Flavell RA, Milbrandt J, Homer RJ and Elias JA: Early growth response gene 1-mediated apoptosis is essential for transforming growth factor β₁-induced pulmonary fibrosis. J Exp Med. 200:377–389. 2004.PubMed/NCBI
11	Parra E and Ferreira J: The effect of siRNA- Egr-1 and camptothecin on growth and chemosensitivity of breast cancer cell lines. Oncol Rep. 23:1159–1165. 2010. View Article : Google Scholar : PubMed/NCBI
12	Baron V, Adamson ED, Calogero A, Ragona G and Mercola D: The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFβ1, PTEN, p53 and fibronectin. Cancer Gene Ther. 13:115–124. 2006.PubMed/NCBI
13	Shaul Y and Ben-Yehoyada M: Role of c-Abl in the DNA damage stress response. Cell Res. 15:33–35. 2005. View Article : Google Scholar : PubMed/NCBI
14	Kharbanda S, Ren R, Pandey P, Shafman TD, Feller SM, Weichselbaum RR and Kufe DW: activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents. Nature. 376:785–788. 1995. View Article : Google Scholar : PubMed/NCBI
15	Pandey P, Raingeaud J, Kaneli M, Weichselbaum RR, Davis RJ, Kufe D and Kharbanda S: Activation of p38 mitogen-activated protein kinase by c-Abl-dependent and independent mechanisms. J Biol Chem. 271:23775–23779. 1996. View Article : Google Scholar : PubMed/NCBI
16	Cong F and Goff SP: c-Abl-induced apoptosis, but not cell cycle arrest, requires mitogen-activated protein kinase kinase 6 activation. Proc Natl Acad Sci USA. 96:13819–13824. 1999. View Article : Google Scholar : PubMed/NCBI
17	Stuart JR, Kawai H, Tsai KK, Chuang EY and Yuan ZM: c-Abl regulates early growth response protein (EGR1) in response to oxidative stress. Oncogene. 24:8085–8092. 2005.PubMed/NCBI
18	Daniels CE, Wilkes MC, Edens M, Kottom TJ, Murphy SJ, Limper AH and Leof EB: Imatinib mesylate inhibits the profibrogenic activity of TGF-β and prevents bleomycin-mediated lung fibrosis. J Clin Invest. 114:1308–1316. 2004.PubMed/NCBI
19	Welch PJ and Wang JY: Abrogation of retinoblastoma protein functions by c-Abl through tyrosine kinase-dependent and -independent mechanisms. Mol Cell Biol. 15:5542–5551. 1995.PubMed/NCBI
20	Barilà D, Rufini A, Condò I, Ventura N, Dorey K, Superti-Furga G and Testi R: Caspase-dependent cleavage of c-Abl contributes to apoptosis. Mol Cell Biol. 23:2790–2799. 2003.PubMed/NCBI
21	Machuy N, Rajalingam K and Rudel T: Requirement of caspase-mediated cleavage of c-Abl during stress-induced apoptosis. Cell Death Differ. 11:290–300. 2004. View Article : Google Scholar : PubMed/NCBI
22	Huang DY, Chao Y, Tai MH, Yu YH and Lin WW: STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death. J Biomed Sci. 19:352012. View Article : Google Scholar : PubMed/NCBI
23	Li B, Cong F, Tan CP, Wang SX and Goff SP: Aph2, a protein with a zf-DHHC motif, interacts with c-Abl and has pro-apoptotic activity. J Biol Chem. 277:28870–28876. 2002.PubMed/NCBI
24	Abdulkadir SA, Carbone JM, Naughton CK, Humphrey PA, Catalona WJ and Milbrandt J: Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma. Hum Pathol. 32:935–939. 2001. View Article : Google Scholar : PubMed/NCBI
25	Lucerna M, Mechtcheriakova D, Kadl A, Schabbauer G, Schäfer R, Gruber F, Koshelnick Y, Müller HD, Issbrücker K, Clauss M, Binder BR and Hofer E: NAB2, a corepressor of EGR-1, inhibits vascular endothelial growth factor-mediated gene induction and angiogenic responses of endothelial cells. J Biol Chem. 278:11433–11440. 2003. View Article : Google Scholar : PubMed/NCBI
26	Parra E: Inhibition of JNK-1 by small interference RNA induces apoptotic signalling in PC-3 prostate cancer cells. Int J Mol Med. 30:923–930. 2012.PubMed/NCBI
27	Parra E and Gutiérrez L: Growth inhibition of Tax-activated human Jurkat leukemia T cells by all-trans retinoic acid requires JNK-1 inhibition. Oncol Rep. 29:387–393. 2013.PubMed/NCBI
28	Krones-Herzig A, Mittal S, Yule K, Liang H, English C, Urcis R, Soni T, Adamson ED and Mercola D: Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res. 65:5133–5143. 2005. View Article : Google Scholar : PubMed/NCBI
29	Calogero A, Arcella A, De Gregorio G, Porcellini A, Mercola D, Liu C, Lombari V, Zani M, Giannini G, Gagliardi FM, Caruso R, Gulino A, Frati L and Ragona G: The early growth response gene EGR-1 behaves as a suppressor gene that is down-regulated independent of ARF/Mdm2 but not p53 alterations in fresh human gliomas. Clin Cancer Res. 7:2788–2796. 2001.
30	Egerod FL, Bartels A, Fristrup N, Borre M, Ørntoft TF, Oleksiewicz MB, Brünner N and Dyrskj⊘t L: High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression. BMC Cancer. 9:3852009. View Article : Google Scholar : PubMed/NCBI
31	Svaren J, Ehrig T, Abdulkadir SA, Ehrengruber MU, Watson MA and Milbrandt J: EGR1 target genes in prostate carcinoma cells identified by microarray analysis. J Biol Chem. 275:38524–38531. 2000. View Article : Google Scholar : PubMed/NCBI
32	Gitenay D and Baron VT: Is EGR1 a potential target for prostate cancer therapy? Future Oncol. 5:993–1003. 2009. View Article : Google Scholar : PubMed/NCBI
33	Suzuki J, Sukezane T, Akagi T, Georgescu MM, Ohtani M, Inoue H, Jat PS, Goff SP, Hanafusa H and Shishido T: Loss of c-abl facilitates anchorage-independent growth of p53- and RB-deficient primary mouse embryonic fibroblasts. Oncogene. 23:8527–8534. 2004.
34	Taagepera S, McDonald D, Loeb JE, Whitaker LL, McElroy AK, Wang JY and Hope TJ: Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA. 95:7457–7462. 1998. View Article : Google Scholar : PubMed/NCBI
35	Ling X, Ma G, Sun T, Liu J and Arlinghaus RB: Bcr and Abl interaction: oncogenic activation of c-Abl by sequestering Bcr. Cancer Res. 63:298–308. 2003.PubMed/NCBI
36	Furstoss O, Dorey K, Simon V, Barilà D, Superti-Furga G and Roche S: c-Abl is an effector of Src for growth factor-induced c-myc expression and DNA synthesis. EMBO J. 21:514–524. 2002. View Article : Google Scholar : PubMed/NCBI
37	Baron V, De Gregorio G, Krones-Herzig A, Virolle T, Calogero A, Urcis R and Mercola D: Inhibition of Egr-1 expression reverses transformation of prostate cancer cells in vitro and in vivo. Oncogene. 22:4194–4204. 2003. View Article : Google Scholar : PubMed/NCBI