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  • Oncogenomics
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Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells

Oncogene volume 25, pages 7311–7323 (2006)Cite this article

Abstract

Progression of prostate cancer to androgen independence is suspected to involve the androgen and protein kinase A (PKA) signaling pathways. Here for the first time, the transcriptomes associated with each pathway and common transcriptional targets in response to stimulation of both pathways were identified in human prostate cancer cells using Affymetrix GeneChip technology (Human Genome U133 plus2). Statistically significant changes in the levels of 858 genes in response to androgen and 303 genes in response to activation of the PKA pathway were determined using GeneSpring software. Expression of a subset of these genes (22) that were transcriptional targets for the androgen and/or PKA pathways were validated by reverse transcriptase–polymerase chain reaction and Western blot analyses. Application of small interfering RNAs to the androgen receptor (AR) revealed that in addition to KLK3, levels of expression of KLK2 and SESN1 were regulated by AR activated by both the androgen and PKA signaling pathways. SESN1 was identified as a gene repressed by activated AR. These results provide a broad view of the effects of the androgen and PKA signaling pathways on the transcriptional program of prostate cancer cells and indicate that only a limited number of genes are targeted by cross-talk between AR and PKA pathways.

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References

  • Agus DB, Cordon-Cardo C, Fox W, Drobnjak M, Koff A, Golde DW et al. (1999). J Natl Cancer Inst 91: 1869–1876.

  • Amler LC, Agus DB, LeDuc C, Sapinoso ML, Fox WD, Kern S et al. (2000). Cancer Res 60: 6134–6141.

  • Bang YJ, Pirnia F, Fang WG, Kang WK, Sartor O, Whitesell L et al. (1994). Proc Natl Acad Sci USA 91: 5330–5334.

  • Bouchal J, Baumforth KR, Svachova M, Murray PG, von Angerer E, Kolar Z . (2005). J Pharm Pharmacol 57: 83–92.

  • Chen T, Cho RW, Stork PJ, Weber MJ . (1999). Cancer Res 59: 213–218.

  • Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, Trapman J . (1996). J Biol Chem 271: 6379–6388.

  • Cox ME, Deeble PD, Bissonette EA, Parsons SJ . (2000). J Biol Chem 275: 13812–13818.

  • Culig Z, Hobisch A, Hittmair A, Cronauer MV, Radmayr C, Zhang J et al. (1997). Prostate 32: 106–114.

  • Daga A, Micol V, Hess D, Aebersold R, Attardi G . (1993). J Biol Chem 268: 8123–8130.

  • Daniel PB, Walker WH, Habener JF . (1998). Annu Rev Nutr 18: 353–383.

  • Day CL, Puthalakath H, Skea G, Strasser A, Barsukov I, Lian LY et al. (2004). Biochem J 377: 597–605.

  • Debes JD, Tindall DJ . (2004). N Engl J Med 351: 1488–1490.

  • DePrimo SE, Diehn M, Nelson JB, Reiter RE, Matese J, Fero M et al. (2002). Genome Biol 3: RESEARCH0032.

  • Dotzlaw H, Moehren U, Mink S, Cato AC, Iniguez Lluhi JA, Baniahmad A . (2002). Mol Endocrinol 16: 661–673.

  • Farini D, Puglianiello A, Mammi C, Siracusa G, Moretti C . (2003). Endocrinology 144: 1631–1643.

  • Gobert GN, Hueser CN, Curran EM, Sun QY, Glinsky VV, Welshons WV et al. (2001). Histochem Cell Biol 115: 381–395.

  • Goldstein JL, Brown MS . (1990). Nature 343: 425–430.

  • Holzbeierlein J, Lal P, LaTulippe E, Smith A, Satagopan J, Zhang L et al. (2004). Am J Pathol 164: 217–227.

  • Horoszewicz JS, Leong SS, Chu TM, Wajsman ZL, Friedman M, Papsidero L et al. (1980). Prog Clin Biol Res 37: 115–132.

  • Huggins C, Hodges CV . (2002). J Urol 168: 9–12.

  • Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A et al. (2005). CA Cancer J Clin 55: 10–30.

  • Jung M, Romer A, Keyszer G, Lein M, Kristiansen G, Schnorr D et al. (2003). Prostate 55: 89–98.

  • Kemppainen JA, Lane MV, Sar M, Wilson EM . (1992). J Biol Chem 267: 968–974.

  • Lee C, Sutkowski DM, Sensibar JA, Zelner D, Kim I, Amsel I et al. (1995). Endocrinology 136: 796–803.

  • Morris DI, Robbins JD, Ruoho AE, Sutkowski EM, Seamon KB . (1991). J Biol Chem 266: 13377–13384.

  • Nakhla AM, Leonard J, Hryb DJ, Rosner W . (1999). Steroids 64: 213–216.

  • Nantermet PV, Xu J, Yu Y, Hodor P, Holder D, Adamski S et al. (2004). J Biol Chem 279: 1310–1322.

  • Nazareth LV, Weigel NL . (1996). J Biol Chem 271: 19900–19907.

  • Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J et al. (2002). Proc Natl Acad Sci USA 99: 11890–11895.

  • Prins GS . (2000). Mayo Clin Proc 75(Suppl): S32–S35.

  • Riegman PH, Vlietstra RJ, van der Korput JA, Brinkmann AO, Trapman J . (1991). Mol Endocrinol 5: 1921–1930.

  • Robles LD, Frost AR, Davila M, Hutson AD, Grizzle WE, Chakrabarti R . (2002). J Biol Chem 277: 25431–25438.

  • Roche PJ, Hoare SA, Parker MG . (1992). Mol Endocrinol 6: 2229–2235.

  • Rokhlin OW, Taghiyev AF, Guseva NV, Glover RA, Chumakov PM, Kravchenko JE et al. (2005). Oncogene 24: 6773–6784.

  • Sadar MD, Akopian VA, Beraldi E . (2002). Mol Cancer Ther 1: 629–637.

  • Sadar MD, Hussain M, Bruchovsky N . (1999). Endocr Relat Cancer 6: 487–502.

  • Sadar MD . (1999). J Biol Chem 274: 7777–7783.

  • Schuur ER, Henderson GA, Kmetec LA, Miller JD, Lamparski HG, Henderson DR . (1996). J Biol Chem 271: 7043–7051.

  • Segawa T, Nau ME, Xu LL, Chilukuri RN, Makarem M, Zhang W et al. (2002). Oncogene 21: 8749–8758.

  • Shah GV, Rayford W, Noble MJ, Austenfeld M, Weigel J, Vamos S et al. (1994). Endocrinology 134: 596–602.

  • Shenk JL, Fisher CJ, Chen SY, Zhou XF, Tillman K, Shemshedini L . (2001). J Biol Chem 276: 38472–38479.

  • Sramkoski RM, Pretlow II TG, Giaconia JM, Pretlow TP, Schwartz S, Sy MS et al. (1999). In vitro Cell Dev Biol Anim 35: 403–409.

  • Stroud RM, Walter P . (1999). Curr Opin Struct Biol 9: 754–759.

  • Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ . (2001). Genes Dev 15: 1796–1807.

  • Tasken K, Aandahl EM . (2004). Physiol Rev 84: 137–167.

  • Tepper CG, Boucher DL, Ryan PE, Ma AH, Xia L, Lee LF et al. (2002). Cancer Res 62: 6606–6614.

  • Tusher VG, Tibshirani R, Chu G . (2001). Proc Natl Acad Sci USA 98: 5116–5121.

  • van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL et al. (2003). Prostate 57: 205–225.

  • Van Patten SM, Ng DC, Th'ng JP, Angelos KL, Smith AJ, Walsh DA . (1991). Proc Natl Acad Sci USA 88: 5383–5387.

  • Velasco-Miguel S, Buckbinder L, Jean P, Gelbert L, Talbott R, Laidlaw J et al. (1999). Oncogene 18: 127–137.

  • Vilaboa N, Bermejo R, Martinez P, Bornstein R, Cales C . (2004). Nucl Acids Res 32: 6454–6467.

  • Waghray A, Feroze F, Schober MS, Yao F, Wood C, Puravs E et al. (2001). Proteomics 1: 1327–1338.

  • Wang G, Sadar MD . (2006). J Cell Biochem 98: 36–53.

  • Wright ME, Tsai MJ, Aebersold R . (2003). Mol Endocrinol 17: 1726–1737.

  • Xu LL, Su YP, Labiche R, Segawa T, Shanmugam N, McLeod DG et al. (2001). Int J Cancer 92: 322–328.

  • Yan Z, DeGregori J, Shohet R, Leone G, Stillman B, Nevins JR et al. (1998). Proc Natl Acad Sci USA 95: 3603–3608.

  • Young CY, Andrews PE, Montgomery BT, Tindall DJ . (1992). Biochemistry 31: 818–824.

  • Young CY, Montgomery BT, Andrews PE, Qui SD, Bilhartz DL, Tindall DJ . (1991). Cancer Res 51: 3748–3752.

  • Zeng C . (2000). Microsc Res Tech 49: 467–477.

  • Zhang M, Magit D, Sager R . (1997). Proc Natl Acad Sci USA 94: 5673–5678.

  • Zhou ZX, Lane MV, Kemppainen JA, French FS, Wilson EM . (1995). Mol Endocrinol 9: 208–218.

  • Zou Z, Gao C, Nagaich AK, Connell T, Saito S, Moul JW et al. (2000). J Biol Chem 275: 6051–6054.

  • Zou Z, Zhang W, Young D, Gleave MG, Rennie P, Connell T et al. (2002). Clin Cancer Res 8: 1172–1177.

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Acknowledgements

We thank Nasrin Mawji, Heidi Hare and Jean Wang for their technical assistance. This work is supported by funding from NIH, Grant CA105403 (MDS). MAM and SJMJ are scholars of the Michael Smith Foundation for Health Research. MAM is a Terry Fox Young Investigator.

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  1. Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, Canada

    G Wang, S J M Jones, M A Marra & M D Sadar

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  1. G Wang
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Correspondence to M D Sadar.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Wang, G., Jones, S., Marra, M. et al. Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene 25, 7311–7323 (2006). https://doi.org/10.1038/sj.onc.1209715

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