Effects of sex steroids on cell growth and C-myc oncogene expression in LN-CaP and DU-145 prostatic carcinoma cell lines

Abstract

The prostate gland is dependent on androgens for the maintenance of its normal growth and functional integrity. Initially, growth of the majority of prostate tumours can be manipulated by endocrine therapy. In the present study, we evaluated the effects of sex steroids on the cell growth and expression of the C-myc oncogene in two human prostatic adenocarcinoma cell lines. We found that dihydrotestosterone increases the proliferation rate of prostatic cells, and amplification of C-myc oncogene is hormone-dependent. We also demonstrated a positive correlation between the number of cells positive for C-myc oncogene and oncoprotein in hormone-treated prostate cell lines.

Clinicopathologic Correlation of Up-regulated Genes Identified Using cDNA Microarray and Real-time Reverse Transcription-PCR in Human Colorectal Cancer

“…This suggests a gender-related influence on c-MYC expression. The role of androgen in increasing c-MYC expression has been investigated and confirmed in prostatic cancer by many authors (9)(10)(11)(12). Therefore, it is likely that androgen may have a similar effect in colorectal cancer.…”

Myc confers androgen-independent prostate cancer cell growth

“…The mechanism of c-myc regulation by AR is unclear, but our data suggest that c-myc is regulated at a posttranscriptional level since mRNA levels remained unchanged. It has been suggested in the literature that there is a shift from an inhibitory effect of AR on c-myc expression in cells in which AR induces differentiation (31,32) to an activator effect in cells in which AR induces proliferation (33,34).…”

Effects of 5 alpha reductase inhibitors on androgen-dependent human prostatic carcinoma cells

“…In addition, some effects of 5aR inhibitors could be mediated by estrogens which are synthesized by the enzyme aromatase present in epithelial cells. Epidemiological and experimental studies suggest that estrogens may have both cancerogenic and chemopreventive effects in the prostatic epithelium (Asadi and Sharifi 1995;Corey et al 2002: Ye et al 2001). These divergent effects may reflect the presence of two distinct receptors, the estrogen receptors alpha (ERa) and beta (ERb), which can homodimerize and heterodimerize to form a signaling dimeric complex or heterodimerize with AR and activate PTK pathways.…”

“…However, the presence of ERa in prostatic malignancies appears to be a late event in tumor progression because the most significant levels have been detected in metastatic and androgeninsensitive lesions. Then, intracellular conversion of androgens to estrogens may contribute both to the etiopathogenesis and to progression of PCa (Asadi and Sharifi 1995;Corey et al 2002;Ye et al 2001). The recent identification of the T metabolite 5a-androstane3b,17b-diol as a specific ligand of ER-b in rat ventral prostate tissue (Maggiolini et al 2002), further supports the hypothesis of a relevant role played by ER signaling in prostate pathophysiology.…”

“…ERb mRNA, ERb immunoreactivity, and estrogen binding sites have been reported to be present in PCa tissues (Fixemer et al 2003;Linja et al 2003) as well as in PCa cell lines (Negri-Cesi et al 1999) and xenografts (Corey et al 2002). The possibility that E2 might be formed within malignant prostate cells from T by Aro might assume a pathological relevance, particularly in androgen-independent PCa (Asadi and Sharifi 1995). The presence of Aro and its relevance for the development and/or maintenance of prostate tumors are still open and controversial questions (Modugno et al 2001;Negri-Cesi et al 1999;Smith et al 2002).…”