Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conjugation of gonadotropin-releasing hormone (GnRH) analogues GnRH-III, MI-1544, and MI-1892 through lysyl side chains and a tetrapeptide spacer, Gly-Phe-Leu-Gly (X) to a copolymer, poly(N-vinylpyrrolidone-co-maleic acid) (P) caused increased antiproliferative activity toward MCF-7 and MDA-MB-231 breast, PC3 and LNCaP prostate, and Ishikawa endometrial cancer cell lines in culture and against tumor development by xenografts of the breast cancer cells in immunodeficient mice. MCF-7 cells treated with P-X-1544 and P-X-1892 displayed characteristic signs of apoptosis, including vacuoles in the cytoplasm, rounding up, apoptotic bodies, bleb formation, and DNA fragmentation. Conjugates, but not free peptides, inhibited cdc25 phosphatase and caused accumulation of Ishikawa and PC3 cells in the G2/M phase of the cell cycle after 24 h at lower doses and in the G1 and G2 phases after 48 h. Since P-X-peptides appear to be internalized, the increased cytotoxicity of the conjugates is attributed to protection of peptides from proteolysis, enhanced interaction of the peptides with the GnRH receptors, and/or internalization of P-X-peptide receptor complexes so that P can exert toxic effects inside, possibly by inhibiting enzymes involved in the cell cycle. The additional specificity of P-X-peptides compared with free peptides for direct antiproliferative effects on the cancer cells but not for interactions in the pituitary indicates the therapeutic potential of the conjugates.
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PMID:Gonadotropin-releasing hormone analogue conjugates with strong selective antitumor activity. 1005 47

The strategy of therapy and prognosis of reproductive system neoplasia generally depend on the steroid receptor status of tumor. The causes of formation of steroid receptor-free tumors are to be investigated. The genetic polymorphism of CYP19 (aromatase), CYP17 (17-hydroxylase; 17,20-lyase), CYP1B1 (4-estrogen hydroxylase) and COMT (catechol-O-methyl transferase) was studied in a total of 254 patients with breast and endometrial cancer, with particular reference to the association of certain polymorphisms and receptor status of tumor. It was found that the lack of estrogen receptor (ER) in breast tumor was due to a deficit in the A3A6 allele (p(0.01), while the absence of progesterone receptors was associated with a lower incidence of the A1A1 and A1A2 variants (p = 0.022) of tetranucleotide repeats in the CYP19 gene. In the same patients, receptor-negative tumors occurred more often (p = 0.032) than in combinations of higher level of 4-hydroxylase estradiol of S-allele in position 48 (Gly/Arg) of the CYP1B1 gene. Moreover, endometrial carcinoma patients tended to reveal (p = 0.058) an increased ratio of A6A7-CYP19 to allele A1-containing variant. No other distinctions between R(+) and R(-) tumors were identified. It is suggested that peculiar polymorphisms of steroidogenic enzymes may moderately influence the genesis of R(-) neoplasms which may be associated with either the rate of estrogen biosynthesis or, as in the case of CYP1B1, with formation of genotoxic derivatives of estrogens. The latter point is to be investigated further.
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PMID:[Genetic polymorphism of steroidogenic enzymes and steroid receptor level in tumors of the reproductive system]. 1517 18

The Cytochrome P450 1B1 (CYP1B1) is one of the major CYP450 enzymes catalyzing 4-hydroxylation, an important elimination step for estrogens. Relatively little is known, however, about the impact of this gene on the onset and cessation of menstruation, which are significant milestones in a woman's life and predictors of many hormone related diseases. In this report, we described the association of four SNPs in the CYP1B1 gene, Arg48Gly, Ala119Ser, Leu432Val, and Asp449Asp, with the ages of menarche and menopause, years of menstruation and total number of menstrual cycles. Included in the study were 1958 community controls from two recently completed population-based case-control studies of breast cancer and endometrial cancer. No association was observed between the CYP1B1 polymorphisms and the age of menarche among either pre- or post-menopausal women. Among the women who experienced natural menopause, the three non-synonymous SNPs were significantly associated with menopausal age, years of menstruation, and total number of menstrual cycles. The Gly and Ser alleles of Arg48Gly and Ala119Ser were associated with later menopause, more years of menstruation and more menstrual cycles, while women with allele Val at Leu432Val had a 0.9 year earlier menopause, 1.0 year shorter reproductive span, and 12.6 fewer menstrual cycles than those women without this allele. In conclusion, the results from this study suggested that CYP1B1 genetic polymorphisms may be associated with the natural onset of menopause.
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PMID:Polymorphisms of the CYP1B1 gene may be associated with the onset of natural menopause in Chinese women. 1676 47

The decapeptide GnRH is known for its central role in the regulation of the hypothalamo-pituitary-gonadal axis. In addition, it is also known to have local effects within peripheral tissues. The zinc metalloendopeptidase, EC 3.4.24.15 (EP24.15), can cleave GnRH at the Tyr(5)-Gly(6) bond to form the pentapeptide, GnRH-(1-5). The central and peripheral effect of GnRH-(1-5) is different from its parent peptide, GnRH. In the current study, we examined the effect of GnRH-(1-5) on epidermal growth factor receptor (EGFR) phosphorylation and cellular migration. Using the Ishikawa cell line as a model of endometrial cancer, we demonstrate that GnRH-(1-5) stimulates epidermal growth factor release, increases the phosphorylation of EGFR (P < .05) at three tyrosine sites (992, 1045, 1068), and promotes cellular migration. In addition, we also demonstrate that these actions of GnRH-(1-5) are mediated by the orphan G protein-coupled receptor 101 (GPR101). Down-regulation of GPR101 expression blocked the GnRH-(1-5)-mediated release of epidermal growth factor and the subsequent phosphorylation of EGFR and cellular migration. These results suggest that GPR101 is a critical requirement for GnRH-(1-5) transactivation of EGFR in Ishikawa cells.
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PMID:GnRH-(1-5) transactivates EGFR in Ishikawa human endometrial cells via an orphan G protein-coupled receptor. 2426 76