Beta-catenin is involved in insulin-like growth factor 1-mediated transactivation of the androgen receptor.
The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. IGF-I and other polypeptide growth factors have been shown to be capable of induction of androgen receptor (AR) activation in the absence of, or at low levels of, ligand. It has been shown that IGF-I increases the cellular level of beta-catenin, an AR coactivator. In this study, we performed several experiments to test whether beta-catenin is involved in IGF-I-induced AR-mediated transcription. We demonstrate that IGF-I enhances the expression of endogenous prostate-specific antigen, an AR target gene, and elevates the level of cytoplasmic and nuclear beta-catenin in prostate cancer cells. Transfection of either wild-type or a constitutively active mutant of the IGF-I receptor augments AR-mediated transcription. An antisense construct of beta-catenin that decreases the cellular level of beta-catenin can reduce IGF-1 receptor-mediated enhancement of AR activity. Moreover, using a pulse-chase experiment, we showed that IGF-I enhances the stability of beta-catenin in prostate cancer cells. Our findings delineate a novel pathway for IGF-I in modulating androgen signaling through beta-catenin.
Verras
Meletios
M
Department of Urology, R135, Edwards Building, Stanford University School of Medicine, Stanford, California 94305-5328, USA.
Sun
Zijie
Z
D000818:Animals; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000737:chemistry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008024:Ligands; D008156:Luciferases / Q000378:metabolism; D008297:Male; D009154:Mutation; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D051176:beta Catenin; D001616:beta-Galactosidase / Q000378:metabolism
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D006133:Growth Substances; D008024:Ligands; D010455:Peptides; D011944:Receptors, Androgen; D015534:Trans-Activators; D051176:beta Catenin; D007334:Insulin-Like Growth Factor I; D008156:Luciferases; D001616:beta-Galactosidase; D017430:Prostate-Specific Antigen