Involvement of up-regulation of 17beta-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers.

Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 +/- 17.5 pg/g) (mean +/- SE) were not significantly different from those of premenopausal patients (110.1 +/- 10.1 pg/g) (p = 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17beta-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17beta-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients.