The analysis of intratumoral estrogen metabolism and production in human breast and endometrial carcinoma

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We have studied intratumoral metabolism and production of estrogens and its biological significance in estrogen dependent neoplasms including human endometrial and breast carcinoma. We first studied the activity and expression of 17β-hydroxysteroid dehydrogenase (HSD) type 1 and 2, involved in the interconversion of estrone and estrodiol. In human breast carcinoma, 17βHSD1 is dominant in both actual carcinoma cases (178 cases) and cell lines derived from breast cancer whereas in human endometrial carcinoma, 17βHSD2 is dominant in both actual carcinoma cases (102 cases) and its cell lines. These results suggest that intratumoral estrogen metabolism and actions is different between human endometrial and breast carcinoma despite the presence of estrogen receptor. We further demonstrated that the expression and activity of these enzymes are regulated by retinoids and progesterones. These results suggest the importance of these as regulators of intratumoral metabolism in these estrogen dependent neoplasms. Therefore, we then examined the expression of retinoid receptors (RAR α β and γ, RXR α β and γ) and progesterone receptors A and B in these tumors. We demonstrated that the presence of these receptors may play important roles in regulation of intratumoral 17β HSDs in human breast and endometrial carcinoma. Other important enzymes involved in intratumoral estrogen metabolism are estrogen sulfatase (STS) and estrogen sulfotransferase (EST). We therefore examined the expression of these two important enzymes in human breast carcinoma. The presence of STS in tumor was significantly associated with large tumor diameters and recurrence but that of EST exerts beneficial effects on the clinical outcome of the patients. The presence of EST turned out to be an independent prognostic factors of breast cancers.