Androgen receptor and c-Myc transcription factors as putative partners in the in vivo cross-talk between androgen receptor-mediated and c-Met-mediated signalling pathways

• Authors: Magdalena Dudkowska , Tomasz Jaworski , Barbara Grzelakowska-Sztabert , Małgorzata Manteuffel-Cymborowska
• Languages of publication: EN

Abstracts

EN

Cross-talk between two signal transduction pathways leads to a negative regulation of androgen-induced ornithine decarboxylase (ODC) gene expression in the mouse kidney. One pathway is triggered by testosterone via the intracellular androgen receptor, AR, and the other is induced by antifolate CB 3717 or folate via hepatocyte growth factor and its cell membrane receptor c-Met. Here we report the studies of the expression of AR and c-Myc transcription factors involved in ODC transactivation. Administration of CB 3717 or folate decreased the expression of AR. In contrast, testosterone did not modify AR mRNA content but augmented the AR protein. Furthermore, we demonstrate that administration of folate, but not testosterone, increases c-Myc transcript and protein level. We also document that activation of both examined pathways does not decrease the testosterone-induced AR protein level, but markedly increases c-Myc protein which is nearly 2-fold up-regulated compared to its level evoked solely by testosterone. We suspect that this pronounced increase of c-Myc protein might have functional consequences mirrored by down-regulated expression of AR target genes, among them ODC.

Keywords

EN

HGF/c-Met; c-Myc; cross-talk; androgen receptor; antifolate/folate-injured kidney

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2007
• Volume: 54
• Issue: 2
• Pages: 253-259

Dates

published

2007

received

2007-03-26

revised

2007-04-23

accepted

2007-05-11

(unknown)

2007-05-23

Contributors

author

Magdalena Dudkowska

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland

author

Tomasz Jaworski

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland

author

Barbara Grzelakowska-Sztabert

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland

author

Małgorzata Manteuffel-Cymborowska

• Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland

References

• Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117: 421-426.
• Adhikary S, Eilers M (2005) Transcriptional regulation and transformation by c-Myc proteins. Nat Rev Mol Cell Biol 6: 635-645.
• Bièche I, Parfait B, Tozlu S, Lidereau R, Vidaud M (2001) Quantitation of androgen receptor gene expression in sporadic breast tumors by real-time RT-PCR: evidence that MYC is an AR-regulated gene. Carcinogenesis 22: 1521-1526.
• Bienz M (2005) β-Catenin: a pivot between cell adhesion and Wnt signaling. Curr Biol 15: R64-R67.
• Dudkowska M, Jaworski T, Zielińska J, Manteuffel-Cymborowska M, Grzelakowska-Sztabert B (2006) Akt kinase and c-Myc are involved in the negative cross-talk between androgen receptor-mediated and c-Met-mediated pathways. In Abstracts of FEBS Special Meeting on Cellular Signaling, pp 82-83, Dubrownik.
• Dudkowska M, Manteuffel-Cymborowska M, Chmurzyńska W, Grzelakowska-Sztabert B (1999) Catecholamines participate in the induction of ornithine decarboxylase gene expression in normal and hyperplastic mouse kidney. Biochim Biophys Acta 1454: 71-79.
• Dudkowska M, Stachurska A, Chmurzyńska W, Grzelakowska-Sztabert B, Manteuffel-Cymborowska M (2001) Cross-talk between steroid-receptor-mediated and cell-membrane-receptor-mediated signalling pathways results in the in vivo modulation of c-Met and ornithine decarboxylase gene expression in mouse kidney. Biochem J 353: 317-323.
• Furutani T, Watanabe T, Tanimoto K, Hashimoto T, Koutoku H, Kudoh M, Shimizu Y, Kato S, Shikama H (2002) Stabilization of androgen receptor protein is induced by agonist, not by antagonists. Biochem Biophys Res Commun 294: 779-784.
• Grad JM, Dai JL, Wu S, Burnstein KL (1999) Multiple androgen response elements and a Myc consensus site in the androgen receptor (AR) coding region are involved in androgen-mediated up-regulation of AR messenger RNA. Mol Endocrinol 13: 1896-1911.
• Gregory MA, Qi Y, Hann SR (2003) Phosphorylation by glycogen synthase kinase-3 controls c-Myc proteolysis and subnuclear localization. J Biol Chem 278: 51606-51612.
• Grumont RJ, Strasser A, Gerondakis S (2002) B cell growth is controlled by phosphatidylinositol 3-kinase-dependent induction of Rel/NF-κB regulated c-myc transcription. Mol Cell 10: 1283-1294.
• He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-Myc as a target of the APC pathway. Science 281: 1509-1512.
• Kane LP, Shapiro VS, Stokoe D, Weiss A (1999) Induction of NF-kappaB by the Akt/PKB kinase. Curr Biol 9: 601-604.
• Kikuchi A (2000) Regulation of β-catenin signaling in the Wnt pathway. Biochem Biophys Res Commun 268: 243-248.
• Law GL, Li RS, Morris DR (1995) Transcriptional control of the ODC gene. In Polyamines: Regulation and Molecular Interaction (Casero RA jr, ed) pp 5-26, RG Landes Company, Austin, Texas
• Lee DK, Chang C (2003) Endocrine mechanisms of disease. Expression and degradation of androgen receptor: mechanism and clinical implication. J Clin Endocrinol Metab 88: 4043-4054.
• Lim K, Yoo JH, Kim KY, Kweon GR, Kwak ST, Hwang BD (1994) Testosterone regulation of proto-oncogene c-myc expression in primary Sertoli cell cultures from prepubertal rats. J Androl 15: 543-550.
• Lin HK, Yeh S, Kang HY, Chang C (2001) Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor. Proc Natl Acad Sci USA 98: 7200-7205.
• Lin HK, Hu YC, Lee DK, Chang C (2004) Regulation of androgen receptor signaling by PTEN (phosphatase and tensin homolog deleted on chromosome 10) tumor suppressor through distinct mechanisms in prostate cancer cells. Mol Endocrinol 18: 2409-2423.
• Manteuffel-Cymborowska M, Chmurzyńska W, Grzelakowska-Sztabert B (1991) Ornithine decarboxylase induction in mouse kidney as indicator of renal damage. Differential nephrotoxic effect of anticancer antifolate drugs. Cancer Lett 59: 237-241.
• Manteuffel-Cymborowska M, Chmurzyńska W, Grzelakowska-Sztabert B (1993) Polyamines in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney. Differential effect of α-difluoromethylornithine. Biochim Biophys Acta 1182: 133-141.
• Manteuffel-Cymborowska M, Pęska M, Chmurzyńska W, Grzelakowska-Sztabert B (1997) Catecholamines are required for androgen-induced ODC expression but not for hypertrophy of mouse kidney. Biochim Biophys Acta 1356: 292-298.
• Matsuda T, Junicho A, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (2001) Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells. Biochem Biophys Res Commun 283: 179-187.
• McKenna NJ, O'Malley BW (2002) Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108: 465-474.
• Mizokami A, Saiga H, Matsui T, Mita T, Sugita A (1992) Regulation of androgen receptor by androgen and epidermal growth factor in a human prostatic cancer cell line, LNCaP. Endocrinol Jpn 39: 235-243.
• Murphy MJ, Wilson A, Trumpp A (2005) More than just proliferation: Myc function in stem cells. Trends Cell Biol 15: 128-137.
• Pelengaris S, Khan M (2003) The many faces of c-MYC. Arch Biochem Biophys 416: 129-136.
• Perissi V, Rosenfeld MG (2005) Controlling nuclear receptors: the circular logic of cofactor cycles. Nat Rev Mol Cell Biol 6: 542-554.
• Silva IS, Morsch DM, Urnauer L, Spritzer PM (2001) Androgen-induced cell growth and c-myc expression in human non-transformed epithelial prostatic cells in primary culture. Endocr Res 27: 153-169.
• Song G, Ouyang G, Bao S (2005) The activation of Akt/PKB signaling pathway and cell survival, J Cell Mol Med 9: 59-71.
• Stachurska A, Dudkowska M, Czopek A, Manteuffel-Cymborowska M, Grzelakowska-Sztabert B (2004) Cisplatin up-regulates the in vivo biosynthesis and degradation of renal polyamines and c-Myc expression. Biochim Biophys Acta 1689: 259-266.
• Supakar PC, Jung MH, Song CS, Chatterjee B, Roy AK (1995) Nuclear factor κB functions as a negative regulator for the rat androgen receptor gene and NF-κB activity increases during the age-dependent desensitization of the liver. J Biol Chem 270: 837-842.
• Taneja SS, Ha S, Swenson NK, Huang HY, Lee P, Melamed J, Shapiro E, Garabedian MJ, Logan SK (2005) Cell-specific regulation of androgen receptor phosphorylation in vivo. J Biol Chem 280: 40916-40924.
• Tobias KE, Shor J, Kahana C (1995) c-Myc and Max transregulate the mouse ornithine decarboxylase promoter through interaction with two downstream CACGTG motifs. Oncogene 11: 1721-1727.
• Wiren KM, Zhang X, Chang C, Keenan E, Orwoll ES (1997) Transcriptional up-regulation of the human androgen receptor by androgen in bone cells. Endocrinology 138: 2291-2300.
• Wolf DA, Herzinger T, Hermeking H, Blaschke D, Hőrz W (1993) Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen. Mol Endocrinol 7: 924-936.
• Wong HY, Burghoorn JA, van Leeuwen M, de Ruiter PE, Schippers E, Blok LJ, Li KW, Dekker HL, de Jong L, Trapman J, Grootegoed JA, Brinkmann AO (2004) Phosphorylation of androgen receptor isoforms. Biochem J 383: 267-276.
• Yang L, Xie S, Jamaluddin S, Altuwaijri S, Ni J, Kim YT, Chen YT, Hu YC, Wang L, Chuang KH, Wu CT, Chang C (2005) Induction of androgen receptor expression by phosphatidylinositol 3-kinase/Akt downstream substrate, FOXO3a, and their roles in apoptosis of LNCaP prostate cancer cells. J Biol Chem 280: 33558-33565
• Yeap BB, Wilce JA, Leedman PJ (2004) The androgen receptor mRNA. BioEssays 26: 672-682.