Introduction/Background Endogenous or exogenous hyperestrogenism plays the leading role in the pathogenesis of endometrial carcinoma. Estrogens stimulate cell proliferation by inducing the synthesis of growth factors and their receptors, including estrogen receptor alpha (ERα or ESR1). Our purpose was to study the expression of genes responsible for estrogen metabolism and reception in intact and tumor tissues of the uterine body.
Methodology Relative gene expression was studied in biopsy tissues (tumor and intact) of the uterus from 27 patients aged 38–72 years with histologically verified endometrial cancer (EC). Relative expression of genetic loci responsible for estrogen metabolism and reception (CYP1A1, CYP1A2, CYP1B1, CYP19A, ESR1, ESR2, GPER, STS, SULT1A and SULT1E1) was determined by RT-qPCR.
Results Patients with G1 tumors showed a significant (p<0.005) increase in the expression of CYP1A1, CYP1A2, CYP1B1, CYP19A, ESR1, ESR2, GPER, STS, SULT1A1 and SULT1E1 genes by 1820%, 845%, 420%, 737%, 198%, 174%, 54%, 746%, 309% and 412% respectively in tumor tissues compared to intact ones. Patients with G2 EC did not have significant changes in the gene expression in tumors compared to normal tissues. Patients with G3 tumors demonstrated a significant (p<0.005) increase in the expression of CYP1A2 (by 90%), CYP19A (by 72%), ESR2 (by 98%), GPER (by 50%), STS (by 130%) and SULT1E1 genes (by 110%).
Conclusion Only patients with G1 endometrial tumors showed a marked increase in the transcriptional activity of genes responsible for: hydroxylation of estradiol at the C-2 and C-4 positions (CYP1A1 and CYP1B1), formation of estrogens from androgens (CYP19A), regulation of the level of nuclear estrogen receptors (SULT1E1 - sulfotransferase genes), ESR1 and 2 and membrane estrogen receptors (GPER), as well as genes responsible for converting steroids to their active form (steroid sulfatase gene, STS).
Disclosure Nothing to disclose.
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