Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that the clinical efficacy of PC-SPES, a dietary supplement used frequently by men diagnosed with androgen-dependent (AD) or androgen-independent (AI) prostate cancer (CaP), is mechanistically attributed to estrogenic components present in the herbal mixture. To test this hypothesis, we compared estradiol (1 nM), potentially an active principle in PC-SPES, with PC-SPES (using an amount equivalent to 1 nM estradiol) on cell proliferation, induction of apoptosis, and regulation of prostate specific genes, PSA and AR, in androgen-responsive LNCaP cells. Cells cultured in steroid-proficient (FBS) or-deficient (CS-FBS) media to simulate hormonal status pre- and post-castration in vivo, were incubated with estradiol or PC-SPES. Proliferation was reduced in PC-SPES treated cells cultured in media supplemented with FBS or CS-FBS; in contrast, addition of estradiol had no effect on proliferation in FBS cultures, and elicited a 45% growth increase in CS-PBS-supplemented cultures. The differential proliferative response of LNCaP cells to PC-SPES vs. estradiol was also supported by changes in PCNA expression, cell viability, cell cycle phase distribution, and induction of apoptosis. Estradiol elicited time-dependent increases in secreted PSA, whereas PC-SPES suppressed PSA secretion, in both culture conditions. In FBS cultures, PC-SPES lowered intracellular AR and PSA by 61% and 17%, respectively, while estradiol increased intracellular PSA, in parallel with a 42% decrease in AR expression. In comparison with cells maintained with CS-FBS, estradiol induced substantial increases in both intracellular PSA and AR, whereas PC-SPES resulted in a smaller increase in intracellular PSA without affecting the expression of AR. These studies show that the antiproliferative and gene modulatory effects of PC-SPES in androgen-dependent human prostate cancer cells are mechanistically and functionally distinct from effects attributable to estradiol.
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PMID:Effects of PC-SPES on proliferation and expression of AR/PSA in androgen-responsive LNCaP cells are independent of estradiol. 1217 83

Human prostate and colon gene-1 (PC-1, also known as PrLZ) is an androgen-regulated, prostate tissue and prostate cancer cells specifically expressed novel gene. The increased expression of PC-1 gene appears to promote prostate cancer cells androgen-dependent (AD) and androgen-independent (AI) growth. To clone and investigate the expression and regulation elements of PC-1 gene may provide insight into the function of PC-1 and develop a new promoter that targets therapeutic genes to the AD and AI prostate cancer cells. The goal of the present study is cloning and characterization of the PC-1 promoter. A series of luciferase constructs that contain various fragments of the PC-1 5'-genomic region were transfected into human prostate cancer cells for promoter transactivation analysis. 5' deletion analysis identified the -1579 bp promoter region was required for the maximal proximal promoter activity; two transcriptional suppression and a positive regulatory region were identified; -4939 bp promoter fragment of the PC-1 gene retained the characteristic of prostate cancer-specific expression and exhibited higher transcription activity than PSA-6 kb promoter in the medium supplemented with steroid-depleted FBS. An androgen response element (ARE) was located in between -345 and -359 bp of the PC-1 5'-untranslated region relative to the translation initiation site. Thus, our studies not only provide molecular basis of PC-1 transcription regulation, but also define a new regulatory sequence that may be used to restrict expression of therapeutic genes to prostate cancer in the prostate cancer gene therapy.
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PMID:Identification and characterization of the novel human prostate cancer-specific PC-1 gene promoter. 1741 5