Kinases can phosphorylate and regulate androgen receptor activity during prostate cancer progression. In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription. Conversely, the glycogen synthase kinase-3 beta inhibitor lithium chloride suppressed the glycogen synthase kinase-3 beta-mediated phosp...

CCAAT/enhancer-binding protein (C/EBP ) is a nuclear transcription factor that regulates cellular growth and differentiation. In this study we demonstrate that C/EBP gene expression is differentially regulated in rat androgen-dependent tissues and human prostate cancer. C/EBP messenger RNA (mRNA) levels were very low in adult rat ventral prostate, epididymis, and testis. In ventral prostate and...

Androgen is essential for the physiological maintenance of the integrity of prostatic epithelial cells, and castration causes the cells to undergo apoptosis. To study the molecular mechanism of androgen-dependent cell growth, we showed that androgen up-regulates the expression of the cyclin-dependent kinase inhibitor p21 (WAF1, CIP1, SDI1, CAP20) gene at both the mRNA and protein levels. Nuclea...

Androgen receptor (AR) plays a central role in prostate cancer, and most patients respond to androgen deprivation therapies, but they invariably relapse with a more aggressive prostate cancer that has been termed hormone refractory or androgen independent. To identify proteins that mediate this tumor progression, gene expression in 33 androgen-independent prostate cancer bone marrow metastases ...

We aim to correlate point mutations in the androgen receptor gene with receptor phenotypes and with clinical phenotypes of androgen resistance. In two families, the external genitalia were predominantly female at birth, and sex-ofrearing has been female. Their androgen receptor mutation changed arginine-839 to histidine. In a third family, the external genitalia were predominantly male at birth...

Testosterone and 5 alpha-dihydrotestosterone (DHT) concentrations in tissue and body fluid were determined in adult male rats to investigate the mode of androgen distribution. The highest concentration of androgen (testosterone + DHT) and the smallest ratio of DHT/testosterone were observed in the intratesticular tissue fluid. The androgen concentration in testicular vein blood was much higher ...

Prostatic adenocarcinomas depend on androgen for growth and survival. First line treatment of disseminated disease exploits this dependence by specifically targeting androgen receptor function. Clinical evidence has shown that androgen receptor is reactivated in recurrent tumors despite the continuance of androgen deprivation therapy. Several factors have been shown to restore androgen receptor...

Mesenchymal stem cells (MSCs) play an important role in the development of human prostate cancer (PCa). However, the role of MSCs in the transformation of androgen-dependent human PCa cells into androgen-independent manner has been poorly understood. In this study, we investigated the underlying mechanism of MSCs in promoting PCa cells from androgen-dependent into androgen-independent manner. F...

Experiments with human prostate cancer cell lines have shown that forced overexpression of the ErbB2-receptor tyrosine kinase (RTK) promotes androgen-independent growth and increases androgen receptor-transcriptional activity in a ligand-independent fashion. To investigate the relationship between ErbB-RTK signaling and androgen in genetically unmanipulated human prostate cancer, we performed b...

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilisation. A point m...