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PSA Secretion (psa + secretion)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity

INTERNATIONAL JOURNAL OF UROLOGY, Issue 1 2005
HIDEKI OUCHI
Abstract Aim:, To clarify the mechanism of the anticancer effect of genistein, we examined the effect of genistein on telomerase activity in prostate cancer cells. We hypothesized that genistein may exert its anticancer effect by modifying telomerase activity in prostate cancer cells. Methods:, Prostate cancer (LNCaP) cells were cultured with genistein and the number of viable cells was counted. Growth medium was also collected to measure prostate-specific antigen (PSA) concentration. Polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay and reverse transcriptase (RT)-PCR analysis were performed to investigate telomerase activity and the expression of human telomerase reverse transcriptase (hTERT), c-myc and p21 mRNA. To examine the possibility that hTERT transcriptional activity is modulated by genistein, transient cell transfection studies were performed by using luciferase reporter assay. Telomere repeat amplification protocol (TRAP) assay and PCR analysis of hTERT were performed in androgen independent cells, DU-145. Results:, Cell growth of LNCaP was inhibited by genistein and PSA secretion was similarly reduced. In TRAP assay, the telomerase activity of LNCaP cells was reduced by genistein. Reverse transcriptase-PCR analysis revealed that the expression of hTERT and c-myc mRNA was down-regulated by genistein, whereas p21 mRNA increased in response to genistein. Luciferase reporter assay revealed that genistein reduced the transcriptional activity of hTERT. In DU-145 cells, telomerase activity and the expression of hTERT mRNA were also reduced by genistein. Conclusion:, The current study elucidated the molecular mechanism of cell growth inhibition by genistein. The antiproliferative effects of genistein seem to be exerted on the hTERT transcriptional activity via different molecular pathways. [source]

Regulation of PSA secretion and survival signaling by calcium-independent phopholipase A2, in prostate cancer cells

THE PROSTATE, Issue 12 2009
Thomas M. Nicotera
Abstract BACKGROUND Serum prostate specific antigen (PSA) levels in prostate cancer patients serve as a useful biomarker for diagnosing and monitoring prostate cancer. Recently, secreted PSA has been characterized as an autocrine survival factor through activation of Akt and induction of AR. In the normal prostate, PSA is secreted in the lumen of prostatic ducts to lyse proteins in the seminal coagulum. METHODS However, the mechanism for constitutive PSA secretion from benign prostate and its transport across the prostate-blood barrier into serum are unknown. Regulation of peptide secretion by iPLA2 -, has been reported in non-prostatic tissue and in prostate tissue iPLA2 -, is reported to be under androgen regulation. We investigated whether iPLA2 plays a role for in PSA secretion by comparing iPLA2 activity and expression in normal prostate epithelial RWPE-1 cells and in LNCaP prostate cancer cells. Expression of the two active iPLA2 -, mRNA splice variants, LH-iPLA2 and SH-iPLA2, were increased and the inhibitory ankyrin-iPLA2 isoform was markedly reduced in LNCaP cells as compared to normal prostate epithelial RWPE-1 cells. RESULTS These changes are consistent with a higher enzymatic activity in LNCaP cells. The iPLA2 -,-specific inhibitor BEL inhibited PSA secretion and induced apoptosis in LNCaP cells. iPLA2 knockdown using SiRNA inhibited PSA secretion, downregulated AR and induced apoptosis. Exogenous PSA suppressed BEL-induced apoptosis and neutralizing anti-PSA antibody blocked the survival effect of PSA. CONCLUSIONS These data indicate that iPLA2 -, participates in regulating PSA secretion and supports the concept that secreted PSA provides an autocrine survival function in LNCaP cells. Prostate 69:1270,1280, 2009. © 2009 Wiley-Liss, Inc. [source]

Overexpression of 5,-reductase type 1 increases sensitivity of prostate cancer cells to low concentrations of testosterone

THE PROSTATE, Issue 6 2009
Lynn N. Thomas
Abstract INTRODUCTION Conversion of testosterone to dihydrotestosterone (DHT) by the enzymes 5,-reductase types 1 (5,R1) and 2 (5,R2) is important for normal and pathological growth of the prostate. The predominant isoenzyme in normal prostate is 5,R2. However, prostate cancer (PCa) development is accompanied by a decrease in 5,R2 and an increase in 5,R1. The biological significance of increased 5,R1 expression is not fully understood. Therefore, the aim of this study was to determine the effect of overexpression of 5,R1 on growth and prostate-specific antigen (PSA) production in PCa cells. MATERIALS AND METHODS LNGK-9 PCa cells, transiently transfected with pTRE-5,R1 or pTRE alone, were cultured in the presence or absence of testosterone at varying concentrations. Cell growth and PSA secretion were measured after 4,6 days. Cyclin E1, Ki67, and PSA mRNA levels were evaluated using RT-PCR after 24 hr of treatment. RESULTS 10 pM testosterone increased growth of pTRE-5,R1 transfectants by 54.1% over cells grown in the absence of testosterone, compared to 25.0% in pTRE transfectants (P,<,0.01). Likewise, PSA secretion was increased by 56-fold in pTRE-5,R1 transfectants treated with 10 pM testosterone, compared to 26-fold in pTRE transfectants (P,<,0.01). At concentrations of testosterone above 10 pM, the stimulatory effect on growth and PSA secretion was not distinguishable between pTRE-5,R1 and pTRE transfectants. CONCLUSIONS These results demonstrate that upregulation of 5,R1 enhances the cellular response to low, but not high, concentrations of testosterone. This explains one mechanism by which castration-recurrent PCa can proliferate in the presence of castrate levels of circulating testosterone. Prostate 69:595,602, 2009. © 2009 Wiley-Liss, Inc. [source]