Biopolym. Cell. 2013; 29(6):499-505.
http://dx.doi.org/10.7124/bc.000840
Molecular Biomedicine
Search for genes – potential markers of aggressiveness and metastasis for human prostate cancer
1Rosenberg E. E., 2Prudnikova T. Y., 1Gerashchenko G. V., 2Grigorieva E. V., 1Kashuba V. I.
  1. State Key Laboratory of Molecular and Cellular Biology
    Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Institute of Molecular Biology and Biophysics, SD RAMS
    2, Timakova Str., Novosibirsk, Russian Federation, 630117

Abstract

Aim. An investigation of the expression levels of 84 cancer-related genes, involved in the main molecular mechanisms of carcinogenesis, in androgen-independent (AI) cell line PC3 compared to androgen-dependent (AD) cell line LNCaP to find markers of the prostate cancer (PC) aggressiveness and metastasis. Methods. Commercial Q-PCR array was used to determine the genes expression levels. Results. Thirty six genes from the total 84 examined changed expression levels in PC3 cell line compared to LNCaP cell line by 4-fold or more times. Increased expression of the genes of angiogenesis (PDGF, TGFB1, THBS1), invasiveness and metastasis (MET, MMP1, PLAU) and anti-apoptotic factors (BCL2, BCL2L1) were detected. Seven genes (MET, MMP1, PLAU, SERPINE1, EPDR1, TGFB1, VEGFA) were selected as potential markers of the PC aggressiveness and metastasis. Conclusions. The expressions of the genes of invasi- veness and metastasis, cell cycle control and apoptosis undergo the greatest changes during transition from AD to AI type of the prostate cancer. The selected genes could serve as potential markers of invasiveness, metastasis and require further investigation.
Keywords: molecular marker, aggressiveness, metastasis, androgen-independent prostate cancer
Full text: (PDF, in Ukrainian)

References

[1] Hogle W. Prostate cancer screening, risk, prevention and prognosis Prostate Cancer / Ed. W. Hogle Pittsburgh: Oncology Nursing Society, 2009:19–33.
[2] Gumulec J., Masarik M., Krizkova S., Hlavna M., Babula P., Hrabec R., Rovny A., Masarikova M., Sochor J., Adam V., Eckschlager T., Kizek R. Evaluation of alpha-methylacyl-CoA racemase, metallothionein and prostate specific antigen as prostate cancer prognostic markers Neoplasma 2012 59, N 2 P. 191–201.
[3] Tai S., Sun Y., Squires J. M., Zhang H., Oh W. K., Liang C. Z., Huang J. PC3 is a cell line characteristic of prostatic small cell carcinoma Prostate 2011 71, N 15:1668–1679.
[4] Geraschenko G. V., Bogatyrova O. O., Rudenko E. E., Kondratov A. G., Gordiyuk V. V., Zgonnyk Y. M., Vozianov O. F., Pavlova T. V., Zabarovsky E. R., Rynditch A. V., Kashuba V. I. Genetic and epigenetic changes of NKIRAS1 gene in human renal cell carcinomas Exp. Oncol 2010 32, N 2:71–75.
[5] Rudenko E. E., Geraschenko G. V., Lapska Y. V., Bogatyrova O. O., Vozianov S. O., Zgonnyk Y. M., Kashuba V. I. Genetic and epigenetic changes of GPX1 and GPX3 in human clear-cell renal cell carcinoma Biopolym. Cell 2013 29, N 5:395–401.
[6] Chiu Y. T., Liu J., Tang K., Wong Y. C., Khanna K. K., Ling M. T. Inactivation of ATM/ATR DNA damage checkpoint promotes androgen induced chromosomal instability in prostate epithelial cells PLoS One 2012 7, N 12 e51108.
[7] Bhatia B., Multani A. S., Patrawala L., Chen X., Calhoun-Davis T., Zhou J., Schroeder L., Schneider-Broussard R., Shen J., Pathak S., Chang S., Tang D. G. Evidence that senescent human prostate epithelial cells enhance tumorigenicity: cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT Int. J. Cancer 2008 122, N 7 P.1483–1495.
[8] Castro E., Goh C., Olmos D., Saunders E., Leongamornlert D., Tymrakiewicz M., Mahmud N. et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer J. Clin. Oncol 2013 31, N 14:1748–1757.
[9] Chiu Y. T., Han H. Y., Leung S. C., Yuen H. F., Chau C. W., Guo Z., Qiu Y., Chan K. W., Wang X., Wong Y. C., Ling M. T. CDC 25A functions as a novel Ar corepressor in prostate cancer cells J. Mol. Biol 2009 385, N 2:446–456.
[10] Kwon Y. W., Chang I. H., Kim K. D., Kim Y. S., Myung S. C., Kim M. K., Kim T. H. Significance of S100A2 and S100A4 expression in the progression of prostate adenocarcinoma Korean J. Urol 2010 51, N 7:456–462.
[11] Vogelstein B., Lane D., Levine A. J. Surfing the p53 network Nature 2000 408, N 6810:307–310.
[12] Lin Y., Fukuchi J., Hiipakka R. A., Kokontis J. M., Xiang J. Upregulation of Bcl-2 is required for the progression of prostate cancer cells from an androgen-dependent to an androgen-independent growth stage Cell Res 2007 17, N 6:531–536.
[13] Huerta-Yepez S., Baritaki S., Baay-Guzman G., Hernandez-Luna M. A., Hernandez-Cueto A., Vega M. I., Bonavida B. Contribution of either YY1 or BclXL-induced inhibition by the NO-donor DETANONOate in the reversal of drug resistance, both in vitro and in vivo. YY1 and BclXL are overexpressed in prostate cancer Nitric Oxide 2013 29:17–24.
[14] Tang Y. Q., Jaganath I., Manikam R., Sekaran S. D. Phyllanthus suppresses prostate cancer cell, PC-3, proliferation and induces apoptosis through multiple signalling pathways (MAPKs, PI3K/ Akt, NFkB, and hypoxia) Evid. Based Complement Alternat. Med 2013 2013:609581.
[15] Kesarwani P., Mandal R. K., Maheshwari R., Mittal R. D. Influence of caspases 8 and 9 gene promoter polymorphism on prostate cancer susceptibility and early development of hormone refractory prostate cancer BJU Int 2011 107, N 3:471–476.
[16] Long Q., Johnson B. A., Osunkoya A. O., Lai Y. H., Zhou W., Abramovitz M., Xia M., Bouzyk M. B., Nam R. K., Sugar L., Stanimirovic A., Williams D. J., Leyland-Jones B. R., Seth A. K., Petros J. A., Moreno C. S. Protein-coding and microRNA biomarkers of recurrence of prostate cancer following radical prostatectomy Am. J. Pathol 2011 179, N 1:46–54.
[17] Zhu Q., Youn H., Tang J., Tawfik O., Dennis K., Terranova P. F., Du J., Raynal P., Thrasher J. B., Li B. Phosphoinositide 3-OH kinase p85alpha and p110beta are essential for androgen receptor transactivation and tumor progression in prostate cancers Oncogene 2008 27, N 33:4569–4579.
[18] Rostad K., Mannelqvist M., Halvorsen O. J., Oyan A. M., Bo T. H., Stordrange L., Olsen S., Haukaas S. A., Lin B., Hood L., Jonassen I., Akslen L. A., Kalland K. H. ERG upregulation and related ETS transcription factors in prostate cancer Int. J. Oncol 2007 30, N 1:19–32.
[19] DU L., Wu W. A mimic of phosphorylated prolactin induces apoptosis by activating AP-1 and upregulating p21/waf1 in human prostate cancer PC3 cells Oncol. Lett 2012 4, N 5 P. 1064–1068.
[20] Miller S. C., Huang R., Sakamuru S., Shukla S. J., Attene-Ramos M. S., Shinn P., Van Leer D., Leister W., Austin C. P., Xia M. Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action Biochem. Pharmacol 2010 79, N 9:1272–1280.
[21] Chen J., Jiao L., Xu C., Yu Y., Zhang Z., Chang Z., Deng Z., Sun Y. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression BMC Cancer 2012 12:593.
[22] Varma R. R., Hector S. M., Clark K., Greco W. R., Hawthorn L., Pendyala L. Gene expression profiling of a clonal isolate of oxaliplatin-resistant ovarian carcinoma cell line A2780/C10 Oncol. Rep 2005 14, N 4:925–932.
[23] Dedhar S., Gray V., Robertson K., Saulnier R. Identification and characterization of a novel high-molecular-weight form of the integrin alpha 3 subunit Exp. Cell Res 1992 203, N 1 P. 270–275.
[24] Tozawa K. Activation of nuclera factor-kappa B and control of the expression of cell adhesion molecules in human prostate cancer cells Nihon Hinyokika Gakkai Zasshi 1996 87, N 9 P. 1082–1091.
[25] Hurt E. M., Chan K., Serrat M. A., Thomas S. B., Veenstra T. D., Farrar W. L. Identification of vitronectin as an extrinsic inducer of cancer stem cell differentiation and tumor formation Stem Cells 2010 28, N 3:390–398.
[26] Nimmrich I., Erdmann S., Melchers U., Chtarbova S., Finke U., Hentsch S., Hoffmann I., Oertel M., Hoffmann W., Muller O. The novel ependymin related gene UCC1 is highly expressed in colorectal tumor cells Cancer Lett 2001 165, N 1:71–79.
[27] Mustafa N., Martin T. A., Jiang W. G. Metastasis tumour suppressor-1 and the aggressiveness of prostate cancer cells Exp. Ther. Med 2011 2, N 1:157–162.
[28] Wu G. J., Varma V. A., Wu M. W., Wang S. W., Qu P., Yang H., Petros J. A., Lim S. D., Amin M. B. Expression of a human cell adhesion molecule, MUC18, in prostate cancer cell lines and tissues Prostate 2001 48, N 4:305–315.
[29] Paulsson J., Sjoblom T., Micke P., Ponten F., Landberg G., Heldin C. H., Bergh J., Brennan D.J., Jirstrom K., Ostman A. Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer Am. J. Pathol 2009 175, N 1:334–341.
[30] Al-Azayzih A., Gao F., Goc A., Somanath P. R. TGFb1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases Biochem. Biophys. Res. Commun 2012 427, N 1:165–170.
[31] Amatangelo M. D., Goodyear S., Varma D., Stearns M. E. c-Myc expression and MEK1-induced Erk2 nuclear localization are required for TGF-beta induced epithelial-mesenchymal transition and invasion in prostate cancer Carcinogenesis 2012 33, N 10:1965–1975.
[32] Firlej V., Mathieu J. R., Gilbert C., Lemonnier L., Nakhle J., Gallou-Kabani C., Guarmit B., Morin A., Prevarskaya N., Delongchamps N. B., Cabon F. Thrombospondin-1 triggers cell migration and development of advanced prostate tumors Cancer Res 2011 71, N 24:7649–7658.
[33] Darrington E., Zhong M., Vo B. H., Khan S. A. Vascular endothelial growth factor A, secreted in response to transforming growth factor-b1 under hypoxic conditions, induces autocrine effects on migration of prostate cancer cells Asian J. Androl 2012 14, N 5:745–751.
[34] Maeda A., Nakashiro K., Hara S., Sasaki T., Miwa Y., Tanji N., Yokoyama M., Hamakawa H., Oyasu R. Inactivation of AR activates HGF/c-Met system in human prostatic carcinoma cells Biochem. Biophys. Res. Commun 2006 347, N 4:1158– 1165.
[35] Bao W., Fu H. J., Jia L. T., Zhang Y., Li W., Jin B. Q., Yao L. B., Chen S. Y., Yang A. G. HER2-mediated upregulation of MMP-1 is involved in gastric cancer cell invasion Arch. Biochem. Biophys 2010 499, N 1–2:49–55.
[36] Cui Y., Niu A., Pestell R., Kumar R., Curran E. M., Liu Y., Fuqua S. A. Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells Mol. Endocrinol 2006 20, N 9:2020–2035.
[37] Seifert M., Welter C., Mehraein Y., Seitz G. Expression of the nm23 homologues nm23-H4, nm23-H6, and nm23-H7 in human gastric and colon cancer J. Pathol 2005 205, N 5:623–632.
[38] Hagelgans A., Menschikowski M., Fuessel S., Nacke B., Arneth B. M., Wirth M. P., Siegert G. Deregulated expression of urokinase and its inhibitor type 1 in prostate cancer cells: role of epigenetic mechanisms Exp. Mol. Pathol 2013 94, N 3:458–465.
[39] Teoh S. S., Whisstock J. C., Bird P. I. Maspin (SERPINB5) is an obligate intracellular serpin J. Biol. Chem 2010 285, N 14 P. 10862–10869.
[40] Eide T., Ramberg H., Glackin C., Tindall D., Tasken K. A. TWIST1, a novel androgen-regulated gene, is a target for NKX31 in prostate cancer cells Cancer Cell Int 2013 13, N 1:4.