Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate tumor initiation and progression to malignancy may involve upregulation of the androgen receptor known to stimulate prostate cell proliferation; other etiologic mechanisms may include dysfunction of the apoptotic pathway but also deregulation in signal transduction and control of the cell cycle in prostate tissue; such abnormalities could arise from overexpression or mutations in a number of oncogenes or down-regulation by inactivating mutations, allelic loss, or other epigenetic mechanisms in tumor suppressor genes. The advantages and drawbacks of various delivery systems (retroviral, adenoviral, liposomes) used for human gene therapy are being considered. Several ex vivo and in vivo as well as cell culture studies are suggested for the therapy of the human prostate cancer using transfer and expression of genes that might be implicated in prostate carcinogenesis especially of the tumor suppressor p53. Expression of suicidal genes in prostate cancer cells using prostate-specific promoter and enhancer elements as well as targeting of the androgen receptor or the insulin-like growth factor genes with triplex technology in prostate cancer cells and their metastases, is expected to be of therapeutic value.
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PMID:Gene therapy of prostate cancer: p53, suicidal genes, and other targets. 917 86

This review provides an overview of the literature on aspects of reproductive endocrinology wherein Asian men may differ from Caucasian, notably, prostatic neoplasm and the sensivity to pharmacological regimens of male contraception. Both genetic and environmental factors, such as nutrition, might be relevant. Asian men residing in Asia seem to be relatively protected from clinical prostatic neoplasm while the prevalence of preclinical prostatic neoplasm is not different. Migration to an area with a higher prevalence reduces this difference but does not undo it. With regard to prostatic neoplasm the following factors have been considered as relevant in Asian men: 1) a reduction in 5 alpha-reductase level, 2) decreased levels of androgenic ketosteroid precursors of 5 alpha-reduced androgen metabolites, 3) the decreased presence of a P53 mutation, 4) a higher CAG-repeat length of the androgen receptor, 5) a possible higher level of physical activity, 6) differences in sexual activity. Furthermore, Asian men respond to a higher degree with azoospermia in response to contraceptive steroids. Possible explanations offered for the more pronounced response to contraceptive steroids are: 1) differences in testicular structure and decreased spermatogenic potential, 2) an earlier and more marked suppression in LH secretion by exogenous androgens. The differences may be due to genetical and/or environmental factors influencing the peripheral testosterone metabolism. Dietary factors such as the higher intake of phytoestrogens in Asians might exert effects on 5 alpha-reductase activity and/or on sex hormone binding globulin (SHBG) levels, thus having an impact on the biological efficacy of circulating androgens.
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PMID:Differences in reproductive endocrinology between Asian men and Caucasian men--a literature review. 1122 31

IGF binding protein (IGFBP)-3 inhibits cell growth and promotes apoptosis by sequestering free IGFs. In addition IGFBP-3 has IGF-independent, proapoptotic, antiproliferative effects on prostate cancer cells in vitro. Expression of the large T-antigen (Tag) under the long probasin promoter (LPB) in LPB-Tag mice results in prostate tumorigenesis. To investigate the IGF-dependent and IGF-independent effects of IGFBP-3 on prostate tumor growth, we crossed LPB-Tag mice with cytomegalovirus (CMVBP-3) and phosphoglycerate kinase (PGKBP-3) mice that overexpress IGFBP-3 under the cytomegalovirus promoter and the phosphoglycerate kinase promoter, respectively, and also I56G/L80G/L81G-mutant IGFBP-3 (PGKmBP-3) mice that express I56G/L80G/L81G-IGFBP-3, a mutant, that does not bind IGF-I but retains IGF-independent proapoptotic effects in vitro. Prostate tumor size and the steady-state level of p53 were attenuated in LPB-Tag/CMVBP-3 and LPB-Tag/PGKBP-3 mice, compared with LPB-Tag/wild-type (Wt) mice. A more marked effect was observed in LPB-Tag/CMVBP-3, compared with LPB-Tag/PGKBP-3, reflecting increased levels of transgene expression in CMVBP-3 prostate tissue. No attenuation of tumor growth was observed in LPB-Tag/PGKmBP-3 mice during the early tumor development, indicating that the inhibitory effects of IGFBP-3 were most likely IGF dependent during the initiation of tumorigenesis. At 15 wk of age, epidermal growth factor receptor expression was increased in LPB-Tag/Wt and LPB-Tag/PGKmBP-3 tissue, compared with LPB-Tag/PGKBP-3. IGF receptor was increased in all transgenic mice, but pAkt expression, a marker of downstream IGF-I action, was increased only in LPB-Tag/Wt and LPB-Tag/PGKmBP-3. After 15 wk of age, a marked reduction in tumor growth was apparent in LPB-Tag/PGKmBP-3 mice, indicating that the IGF-independent effects of IGFBP-3 may be important in inhibiting tumor progression.
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PMID:Insulin-like growth factor (IGF) binding protein-3 attenuates prostate tumor growth by IGF-dependent and IGF-independent mechanisms. 1661 54