Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.36 (caspase-1)
 6,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human chorionic gonadotropin (hCG) inhibits the progression of 7,12-dimethylbenz[a]anthracene (DMBA) induced mammary carcinomas. In order to determine whether this phenomenon was mediated by induction of programmed cell death or apoptosis, 45-day-old virgin Sprague-Dawley rats received 8 mg DMBA/100 g body weight; 20 days later they were injected daily with 100 IU hCG for 40 days (DMBA + hCG group). Age-matched untreated, hCG- and DMBA + saline treated rats were used as controls. Tissues were collected at the time of DMBA administration and at 5, 10, 20 and 40 days of hCG injection. RNA from mammary glands, adenocarcinomas and ovaries was probed for transforming growth factors (TGF) alpha and beta, and the apoptotic genes TRPM2, ICE, bcl2, bcl-XL, bcl-XS, p53 and c-myc. The mammary glands of hCG-treated animals with or without DMBA exhibited elevated expression of TRPM2, ICE, bcl-XS, c-myc and p53; and elevation in the apoptotic index. Mammary adenocarcinomas developed in those animals treated with hCG showed an elevation in the expression of p53, c-myc and ICE genes in comparison with the levels detected in the adenocarcinomas developed by the animals treated with DMBA alone. No significant alterations in the expression of any of the genes tested was observed in ovarian RNAs. These results led us to conclude that hCG induces programmed cell death in the mammary gland initiated in the carcinogenic process, that this process is p53 dependent, and is modulated by c-myc expression. Our data also indicate the possibility that a cell death program dependent on the bcl2 family exists, because of the potential involvement of p53, bcl-XS and Bax in apoptosis. This additional mechanism of tumor inhibition makes hCG treatment a useful approach for the prevention and therapy of breast cancer.
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PMID:Chorionic gonadotropin inhibits rat mammary carcinogenesis through activation of programmed cell death. 932 78

The glycoprotein hormone, human chorionic gonadotropin (hCG) inhibits mammary tumorigenesis through induction of differentiation, and inhibits the proliferation of human breast epithelial cells (HBEC) in vitro. The present study was designed to determine whether the inhibitory effects of hCG was associated with the modulation of apoptotic gene expression. MCF-10F, a normal immortalized HBEC, BP1-E, a benzo(a)pyrene (BP) transformed cell line, and the urothelial cell line T24, were treated with 100 IU/ml of a commercially available preparation of hCG. Cell growth analysis and RNA extraction for determination of apoptotic gene expression were performed at 24 and 120 hrs of hCG treatment. Both hCG-treated and control cells grew at similar rates for the first 24 hours. A significant reduction in the number of viable MCF-10F and BP1-E cells occurred by 120 hours of treatment, whereas the number of both hCG treated and control T24 cells were similar. Northern blot analysis revealed that the 24 hour-hCG treatment induced an elevation in the expression of the apoptotic genes TRPM2, ICE, TGF-beta, p53, bax, and p21WAF1/CIP1 in MCF-10F cells. By 120 hours of treatment MCF-10F cells maintained the same level of gene expression observed at 24 hours, except for a reduction in c-myc and bax. Control cells exhibited an elevation in the expression of TRPM2, TGF-beta, p53, bax, and p21WAF1/CIP1, whose levels became similar to those observed in hCG-treated cells. The 24 hour-treated BP1-E cells showed activation of ICE, bax and p21WAF1/CIP1. However, TRPM2 expression was moderately activated. By 120 hours TRPM2, ICE, TGF-beta, c-myc and p21WAF1/CIP1 were elevated in both treated and control cells except bax which was slightly down-regulated. The levels of bc12 were significantly decreased by hCG treatment. Gene expression was not modified by hCG treatment in T24 cells. Our findings suggest that hCG induced an acceleration in the expression of apoptotic genes, which became evident before detection of cell growth inhibition. Gene activation differed among immortalized, and chemically transformed cells, suggesting that hCG might utilize both p53 dependent and p53 independent pathways for inhibiting cell cycle progression. The importance of these findings lies in the potential use of agents like hCG for the chemoprevention and chemotherapy of breast cancer.
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PMID:Growth inhibition and activation of apoptotic gene expression by human chorionic gonadotropin in human breast epithelial cells. 989 38

It is the purpose of this paper to assess the expression, cellular localization, and hormonal regulation of rat ovarian interleukin (IL)-1beta converting enzyme (ICE), a putative apoptotic marker. In agreement with previous observations ICE transcripts were noted in relatively increased abundance in the thymus, lung, spleen and small intestine. Although ICE transcripts were barely expressed in the untreated, immature rat ovary, they were apparent throughout a simulated estrous cycle. The in vivo expression of ovarian ICE rose gradually from 6 h after ovulation triggering to a peak (1.74-fold increase versus control, P < 0.05) 24 h after human chorionic gonadotropin administration, a marked and significant decrease to baseline being noted 24 h later. To examine the effect of in vitro culture on ovarian ICE gene expression, whole ovarian dispersates from immature rats were cultured without treatment for 72 h. ICE gene expression significantly (P < 0.01) increased to a maximum 24 h post plating (2.55-fold increase as compared with time zero). Treatment with IL-1beta was associated with a small but statistically insignificant increase in ovarian ICE gene expression. Similarly, provision of IL-RA resulted in a modest, albeit statistically insignificant, decrease in ovarian ICE gene expression. Treatment with GnRH (but not FSH, LH or PMSG) significantly (P < 0.05) increased ovarian ICE gene expression (41.5% increase versus control). Treatment with dexamethasone (but not diethylstilbestrol, R5020 or R1881) produced a significant (P < 0.05) 42.3% decrease in ovarian ICE gene expression as compared with untreated controls. Treatment with TNF alpha (but not ET-1, TGF alpha, TGF beta, IGF-I or bFGF) produced a significant (P < 0.01) 2.5-fold increase in ovarian ICE gene expression as compared with untreated controls. Taken together, our present findings: (1) reaffirm the ovarian expression of the ICE gene, (2) document a periovulatory increase in ovarian ICE gene expression, (3) show the inhibitory effect of glucocorticoids in this regard, and (4) establish TNF alpha as an upregulator. Taken together, these findings suggest a role for ovarian ICE either in the context of apoptosis/atresia or in the context of the ovulatory process.
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PMID:Expression and hormonal regulation of rat ovarian interleukin-1beta converting enzyme, a putative apoptotic marker: endocrine- and paracrine-dependence. 1066 Feb 63