Investigation of in situ estrogen metabolism and estrogen responsive gene in endometrial cancer : New aspects of hormone therapy

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In situ estrogen metabolism and synthesis have been considered to play a very important role in the development and progression of human endometrial carcinomas. The correlation between tissue concentrations of estrogens and status of intratumoral enzymes has, however, not been examined in endometrial carcinoma. Therefore, in this study, we examined the concentrations of estrone (E1), estradiol (E2), and testosterone in carcinoma tissue and plasma as well as intratumoral enzymes activities in carcinoma tissues of postmenopausal patients with endometrial carcinoma. The concentrations of E1, E2 and testosterone in endometrial cancer tissue were significantly higher than those in serum. Various types of intratumorall enzymes expression which included 17 β-hydroxysteroid dehydrogenase type 2 (17 β-HSD type 2), 17 β-HSD type 5, steroid sulfatase, estrogen sulfotransferase and aromatase, were observed in endometrial carcinoma. There was a statistically significant inverse correlation between intratumoral estradiol concentration and the level of 17 β-HSD type 2 mRNA. A statistically significant inverse correlation was detected between tumor tissue testosterone and aromatase mRNA expression level. These results suggest that several intratumoral enzymes expression, especially 17 β-HSD type 2 and aromatase, contribute to intratumoral estrogen levels in human endometrial carcinoma. Moreover, our results suggested that in situ abundance of 17 β-HSD type 2 can predict the possible response of patients with endometrial carcinoma to progestogen treatment. In summary, Estrogen biosynthesis pathway in endometrial cancers is quite different from that in breast cancers. Using cDNA microarrays, I investigated estrogen responsive gene expression in breast and endometrial cancer cell lines. I also suggest that there are large amount of differences between breast and endometrial cancers, regarding estrogen responsive gene expression, which are associated with various actions.