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)

Why some women are at increased risk for the development of endometrial carcinoma while taking the antiestrogen tamoxifen (Tam) for breast cancer treatment or prevention is unknown. Various strains of rodents display differences in sensitivity to compounds with estrogenic activity, but whether differences in Tam sensitivity exist in rodent strains has not been investigated. In the present study, we investigated whether rat strain differences in reproductive tract sensitivity to Tam and estrogen exist between Fischer 344 (F344) and Sprague Dawley (SD) rats. Immature (21-23 day; 6/group), ovariectomized F344 and SD rats were treated with vehicle (control), 17beta-estradiol (E2) [1 x 10 (-6) to 1.0 micro g/kg body weight (BW)] or 4-OH tamoxifen (4-OHT) (1 x 10 (-4) to 10 mg/kg BW) for 2 days and then sacrificed on day 3. Reproductive tracts were collected, weighed, and examined for changes in histomorphology and expression of ER and nuclear receptor co-regulators (SRC1, p300, CARM1, GRIP1, SPA, REA and Uba3). Treatment with E (1 x 10(-5) micro g/kg BW) increased ( <0.05) uterine epithelial cell height in F344 but not SD rats, demonstrating increased sensitivity of the F344 strain to E. Conversely, treatment with 1 x 10(-3) mg/kg BW 4-OHT increased ( <0.05) uterine weight and epithelial cell height in SD but not F344 rats, demonstrating that the SD strain is more sensitive to the antiestrogen. Northern and Western blot and immunohistochemical analysis revealed that ER expression levels in the SD and F344 uterus were not different. Expression of receptor co-regulators was higher in the uterus compared to the vagina regardless of strain and higher CARM1 expression was seen in SD uterus compared to F344 rats. Understanding differences in Tam sensitivity may help us to better understand why some women develop endometrial cancer while taking Tam and be beneficial in treatment decisions for breast cancer patients.
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PMID:Strain differences in tamoxifen sensitivity of Sprague-Dawley and Fischer 344 rats. 1239 57

Given that the transcriptional regulatory activity of estrogen receptor (ER) is modulated by its biochemical cofactors, genetic variation within the ER cofactor genes may alter cellular response to estrogen exposure and consequently modify the risk for endometrial cancer. We genotyped 685 tagging SNPs within 60 ER cofactor genes in 564 endometrial cancer cases and 1,510 controls from Sweden, and tested their associations with the risk of endometrial cancer. We investigated the associations of individual SNPs by using a trend test as well as multiple SNPs within a gene or gene complex by using multi-variant association analysis. No significant association was observed for any individual SNPs or genes, but a marginal association of the cumulative genetic variation of the NCOA2 complex as a whole (NCOA2, CARM1, CREBBP, PRMT1 and EP300) with endometrial cancer risk was observed (P(adjusted) = 0.033). However, the association failed to be replicated in an independent European dataset of 1265 cases and 5190 controls (P = 0.71). The results indicate that common genetic variants within ER cofactor genes are unlikely to play a significant role in endometrial cancer risk in European population.
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PMID:Genetic variants in ER cofactor genes and endometrial cancer risk. 2287 22