DNA microarray analysis reveals metastasis-associated genes in rat prostate cancer cell lines
Keywords:
carcinoma, neoplasm metastasis, gene expression, biological markers, extracellular matrix, microarray analysis
Abstract
Introduction. The molecular and cellular mechanisms involved in prostate cancer progression towards a hormone-independent and highly invasive, metastatic phenotype, are not well understood. Cell lines with different metastatic potential, when analyzed by microarray techniques, offer valuable tools for identifying genes associated with the metastatic phenotype.Objectives. Gene expression profiles were compared for two rat prostate cancer cell lines with differing metastatic abilities in order to better characterized molecular underpinnings of the prostate cancer metastatic process.
Materials and methods. Affymetrix arrays were used to analyze gene expression of two rat prostate cancer cell lines, MAT-LyLu and G. Microarray data were analyzed using pathway and functional group analysis. A selected set of genes was subjected to real-time polymerase chain reaction for validating the microarray data.
Results. Microarray data analysis revealed differential expression of genes from a number of signaling and metabolic pathways. Overexpression was detected in 48 genes and underexpression in 59 genes of the MAT-LyLu line compared to the standard G line. Genes were grouped into functional categories, including epithelial-extracellular matrix interaction, cell motility, cell proliferation, and transporters, among others. Many of these genes were not previously associated to prostate cancer metastasis.
Conclusions. Many genes with altered expression associated with a metastatic prostate cancer phenotype were identified. Further validation of these genes in human prostate samples will determine their usefulness as biomarkers for early diagnosis of recurrence or metastasis of prostate cancer, as well as potential therapeutic targets for this disease.
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References
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35. Buchholz M, Biebl A, Neesse A, Wagner M, Iwamura T, Leder G, et al. SERPINE2 (protease nexin I) promotes extracellular matrix production and local invasion of pancreatic tumors in vivo. Cancer Res. 2003;63:4945-51.
36. Chen LM, Zhang X, Chai KX. Regulation of prostasin expression and function in the prostate. Prostate. 2004;59:1-12.
37. Tahir SA, Yang G, Ebara S, Timme TL, Satoh T, Li L, et al. Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer. Cancer Res.2001;61:3882-5.
38. Thompson TC, Timme TL, Li L, Goltsov A. Caveolin-1, a metastasis-related gene that promotes cell survival in prostate cancer. Apoptosis 1999;4:233-7.
39. Inoue G, Horiike N, Onji M. The CD81 expression in liver in hepatocellular carcinoma. Int J Mol Med. 2001;7:67-71.
40. Bienstock RJ, Barrett JC. KAI1, a prostate metastasis suppressor: prediction of solvated structure and interactions with binding partners; integrins, cadherins, and cell-surface receptor proteins. Mol Carcinog. 2001;32:139-53.
2. Dong JT, Rinker-Schaeffer CW, Ichikawa T, Barrett JC, Isaacs JT. Prostate cancer biology of metastasis and its clinical implications. World J Urol. 1996;14:182-9.
3. Dunning WF. Prostate cancer in the rat. Natl Cancer Inst Monogr. 1963;12:351-69.
4. Isaacs JT, Isaacs WB, Feitz WF, Scheres J. Establishment and characterization of seven Dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers. Prostate. 1986;9:261-81.
5. Isaacs JT, Yu GW, Coffey DS. The characterization of a newly identified, highly metastatic variety of Dunning R 3327 rat prostatic adenocarcinoma system: the MAT LyLu tumor. Invest Urol. 1981;19:20-3.
6. Luo J, Sharma N, Seftor EA, De Larco J, Heidger PM, Hendrix MJ, et al. Heterogeneous expression of invasive and metastatic properties in a prostate tumor model. Pathol Oncol Res 1997;3:264-71.
7. Sharma N, Luo J, Kirschmann DA, O'Malley Y, Robbins ME, Akporiaye ET et al. A novel immunological model for the study of prostate cancer. Cancer Res. 1999;59:2271-6.
8. Li C, Wong WH. Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol. 2001;2:RESEARCH0032.
9. Li C, Wong WH. Model-based analysis of oligonucleotide arrays: expression index computation and outlier detection. Proc Natl Acad Sci USA 2001;98:31-6.
10. Dahlquist KD, Salomonis N, Vranizan K, Lawlor SC, Conklin BR. GenMAPP, a new tool for viewing and analyzing microarray data on biological pathways. Nat Genet. 2002;31:19-20.
11. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25:25-9.
12. Rajeevan MS, Ranamukhaarachchi DG, Vernon SD, Unger ER. Use of real-time quantitative PCR to validate the results of cDNA array and differential display PCR technologies. Methods. 2001;25:443-51.
13. Wenger AS, Mickey DD, Hall M, Silverman LM, Mickey GH, Fried FA. In vitro characterization of MAT LyLu: a Dunning rat prostate adenocarcinoma tumor subline. J Urol. 1984;131:1232-6.
14. Poste G, Fidler IJ. The pathogenesis of cancer metastasis. Nature. 1980;283:139-46.
15. LaTulippe E, Satagopan J, Smith A, Scher H, Scardino P, Reuter V, et al. Comprehensive gene expression analysis of prostate cancer reveals distinct transcriptional programs associated with metastatic disease. Cancer Res. 2002;62:4499-506.
16. Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, et al. Delineation of prognostic biomarkers in prostate cancer. Nature. 2001;412:822-6.
17. Nelson PS, Clegg N, Eroglu B, Hawkins V, Bumgarner R, Smith T, et al. The prostate expression database (PEDB): status and enhancements in 2000. Nucleic Acids Res. 2000;28:212-3.
18. Karhadkar SS, Bova GS, Abdallah N, Dhara S, Gardner D, Maitra A, et al. Hedgehog signaling in prostate regeneration, neoplasia and metastasis. Nature. 2004;431:707-12.
19. Yang X, Chen MW, Terry S, Vacherot F, Bemis DL, Capodice J, et al. Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells. Oncogene. 2006;25:3436-44.
20. Hellawell GO, Brewster SF. Growth factors and their receptors in prostate cancer. BJU Int. 2002;89:230-40.
21. Ma PC, Maulik G, Christensen J, Salgia R. c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev. 2003;22:309-25.
22. Hurle RA, Davies G, Parr C, Mason MD, Jenkins SA, Kynaston HG et al. Hepatocyte growth factor/scatter factor and prostate cancer: a review. Histol Histopathol. 2005;20:1339-49.
23. Maulik G, Shrikhande A, Kijima T, Ma PC, Morrison PT, Salgia R. Role of the hepatocyte growth factor receptor, c-Met, in oncogenesis and potential for therapeutic inhibition. Cytokine Growth Factor Rev. 2002;13:41-59.
24. Kim SJ, Johnson M, Koterba K, Herynk MH, Uehara H, Gallick GE. Reduced c-Met expression by an adenovirus expressing a c-Met ribozyme inhibits tumorigenic growth and lymph node metastases of PC3-LN4 prostate tumor cells in an orthotopic nude mouse model. Clin Cancer Res. 2003;9:5161-70.
25. Parr C, Davies G, Nakamura T, Matsumoto K, Mason MD, Jiang WG. The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/ SF variant. Biochem Biophys Res Commun. 2001;285:1330-7.
26. Beviglia L, Kramer RH. HGF induces FAK activation and integrin-mediated adhesion in MTLn3 breast carcinoma cells. Int J Cancer. 1999;83:640-9.
27. Spence HJ, Johnston I, Ewart K, Buchanan SJ, Fitzgerald U, Ozanne BW. Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells. Oncogene. 2000;19:1266-76.
28. van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415:530-6.
29. Amatschek S, Koenig U, Auer H, Steinlein P, Pacher M, Gruenfelder A, et al. Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes. Cancer Res 2004;64:844-56.
30. Borczuk AC, Shah L, Pearson GD, Walter KL, Wang L, Austin JH, et al. Molecular signatures in biopsy specimens of lung cancer. Am J Respir Crit Care Med. 2004;170:167-74.
31. Burton-Wurster N, Liu W, Matthews GL, Lust G, Roughley PJ, Glant TT, et al. TGF beta 1 and biglycan, decorin, and fibromodulin metabolism in canine cartilage. Osteoarthr Cartil. 2003;11:167-76.
32. Hildebrand A, Romaris M, Rasmussen LM, Heinegard D, Twardzik DR, Border WA, et al. Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. Biochem J. 1994;302:527-34.
33. Schostak M, Krause H, Miller K, Schrader M, Weikert S, Christoph F, et al. Quantitative real-time RT-PCR of CD24 mRNA in the detection of prostate cancer. BMC Urol. 2006;6:7.
34. Kristiansen G, Pilarsky C, Pervan J, Sturzebecher B, Stephan C, Jung K, et al. CD24 expression is a significant predictor of PSA relapse and poor prognosis in low grade or organ confined prostate cancer. Prostate. 2004;58:183-92.
35. Buchholz M, Biebl A, Neesse A, Wagner M, Iwamura T, Leder G, et al. SERPINE2 (protease nexin I) promotes extracellular matrix production and local invasion of pancreatic tumors in vivo. Cancer Res. 2003;63:4945-51.
36. Chen LM, Zhang X, Chai KX. Regulation of prostasin expression and function in the prostate. Prostate. 2004;59:1-12.
37. Tahir SA, Yang G, Ebara S, Timme TL, Satoh T, Li L, et al. Secreted caveolin-1 stimulates cell survival/clonal growth and contributes to metastasis in androgen-insensitive prostate cancer. Cancer Res.2001;61:3882-5.
38. Thompson TC, Timme TL, Li L, Goltsov A. Caveolin-1, a metastasis-related gene that promotes cell survival in prostate cancer. Apoptosis 1999;4:233-7.
39. Inoue G, Horiike N, Onji M. The CD81 expression in liver in hepatocellular carcinoma. Int J Mol Med. 2001;7:67-71.
40. Bienstock RJ, Barrett JC. KAI1, a prostate metastasis suppressor: prediction of solvated structure and interactions with binding partners; integrins, cadherins, and cell-surface receptor proteins. Mol Carcinog. 2001;32:139-53.
How to Cite
1.
Reyes I, Tiwari R, Geliebter J, Reyes N. DNA microarray analysis reveals metastasis-associated genes in rat prostate cancer cell lines. biomedica [Internet]. 2007 Jun. 1 [cited 2024 May 11];27(2):192-203. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/215
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