Altered expression of genes involved in progesterone biosynthesis, metabolism and action in endometrial cancerSinreih, Maša ; Hevir-Kene, Neli ; Lanišnik-Rižner, TeaEndometrial cancer (EC) is one of the most common gynecological malignancies worldwide. It is associated with prolonged exposure to estrogens that is unopposed by the protective effects of ... progesterone, which suggests that altered progesterone biosynthesis, metabolism and actions might be implicated in the development of EC. Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium. First, we examined the expression of genes encoding proteins associated with progesterone biosynthesis: steroidogenic acute regulatory protein (STAR); a side chain cleavage enzyme (CYP11A1); and 3?-hydroxysteroid dehydrogenase/ ketosteroid isomerase (HSD3B). There were 1.9-fold and 10.0-fold decreased expression of STAR and CYP11A1, respectively,in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and HSD3B2. Next, we examined expression of genes encoding five progesterone metabolizing enzymes: the 3-keto and 20-ketosteroid reductases (AKR1C1-AKR1C3) and 5?-reductases (SRD5A1and SRD5A2); and the opposing 20?-hydroxysteroid dehydrogenase (HSD17B2). These genes are expressed in EC and adjacent control endometrium. No statistically significant differences were seen in mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1. Expression of HSD17B2 was 3.0-fold increased, and expression of SRD5A2 was 3.7-fold decreased, in EC versus adjacent control endometrium. We also examined mRNA levels of progesterone receptors A and B (PGR), and separately the expression of progesterone receptor B (PR-B). Here we saw 1.8-fold and 2.0-fold lower mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium. Down-regulation of STAR, CYP11A1 and PGR in endometrial cancer may lead to decreased progesterone biosynthesis and actions although the effects on progesterone levels should be further studied.Vir: Enzymology and molecular biology of carbonyl metabolism (Str. 210-217)Vrsta gradiva - prispevek na konferenciLeto - 2013Jezik - angleškiCOBISS.SI-ID - 30307545
Endometrial Neoplasms | Enzymology | Genetics | Progesterone | Biosynthesis | Metabolism | Cytochrome P-450 | 3-Hydroxysteroid Dehydrogenases | Ketone Oxidoreductases | Gene Expression | Citokrom P-450 | Endometrijske novotvorbe | Progesteron | 3-hidroksisteroidne dehidrogenaze | Ketonske oksidoreduktaze | Gensko izražanje
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