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.
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.
Dudkowska
Magdalena
M
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warszawa, Poland.
Jaworski
Tomasz
T
Grzelakowska-Sztabert
Barbara
B
Manteuffel-Cymborowska
Małgorzata
M
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D005493:Folic Acid Antagonists; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D011799:Quinazolines; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013739:Testosterone; D017228:Hepatocyte Growth Factor; C031662:CB 3717; D005492:Folic Acid; D019859:Proto-Oncogene Proteins c-met; D009955:Ornithine Decarboxylase