Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.3 (HSD)
 3,464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A susceptibility gene for hereditary breast-ovarian cancer, BRCA1, has been assigned by linkage analysis to chromosome 17q21. Candidate genes in this region include EDH17B2, which encodes estradiol 17 beta-hydroxysteroid dehydrogenase II (17 beta-HSD II), and RARA, the gene for retinoic acid receptor alpha. We have typed 22 breast and breast-ovarian cancer families with eight polymorphisms from the chromosome 17q12-21 region, including two in the EDH17B2 gene. Genetic recombination with the breast cancer trait excludes RARA from further consideration as a candidate gene for BRCA1. Both BRCA1 and EDH17B2 map to a 6 cM interval (between THRA1 and D17S579) and no recombination was observed between the two genes. However, direct sequencing of overlapping PCR products containing the entire EDH17B2 gene in four unrelated affected women did not uncover any sequence variation, other than previously described polymorphisms. Mutations in the EDH17B2 gene, therefore do not appear to be responsible for the hereditary breast-ovarian cancer syndrome. Single meiotic crossovers in affected women suggest that BRCA1 is flanked by the loci RARA and D17S78.
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PMID:Genetic mapping of the breast-ovarian cancer syndrome to a small interval on chromosome 17q12-21: exclusion of candidate genes EDH17B2 and RARA. 840 1

Retinoids have recently been proposed to modulate estrogenic actions in various sex steroid-dependent neoplasms, but little has been studied in human endometrial disorders. Therefore, in this study, we first examined the immunolocalization of retinoic acid receptor alpha, beta, and gamma, and retinoid X receptor (RXR) alpha, beta, and gamma in 20 normal cycling human endometria, 34 endometrial hyperplasia, and 46 endometrioid endometrial adenocarcinomas. We then correlated these findings with other clinicopathological parameters, especially in the correlation between retinoid receptor subtypes and the status of steroid hormone receptors, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and aromatase. We also then examined the effects of retinoic acid on the expression of 17 beta-HSD type 2 in cell lines derived from endometrial carcinoma using Northern blotting analysis to examine the possible roles of retinoids in in situ endometrial estrogen metabolism. Among these six retinoid receptors examined, RXR gamma immunoreactivity was exclusively detected in the epithelial cells of the secretory phase endometrium but not of the proliferative phase, which was well correlated with 17 beta-HSD type 2 immunolocalization. However, in endometrial hyperplasia, RXR gamma was not correlated with 17 beta-HSD type 2. In endometrioid endometrial adenocarcinoma, there was a statistically significant correlation between 17 beta-HSD type 2 immunoreactivity and RXR gamma labeling index (LI) (P < 0.001) and between RXR gamma LI and progesterone receptor LI (r = 0.501, P = 0.003). A significant inverse correlation was also detected between RXR gamma LI and patient age (r = 0.449, P = 0.015). No statistically significant correlation was obtained between LIs of receptors and other clinicopathological parameters including the status of intratumoral aromatase examined by immunohistochemistry. In the endometrial carcinoma cell line, RL95-2, retinoic acid markedly increased the level of 17 beta-HSD type 2 messenger RNA in a time- and dose-dependent manner. These results all suggest that retinoic acids may be involved in modulation of in situ estrogen metabolism in both normal and neoplastic human endometrium possibly through RXR gamma by stimulating the expression of 17 beta-HSD type 2.
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PMID:Retinoid receptors in the human endometrium and its disorders: a possible modulator of 17 beta-hydroxysteroid dehydrogenase. 1139 77