17-beta-hydroxysteroid dehydrogenase in human breast and endometrial carcinoma. A new development in intracrinology.

Abstract

Intratumoral metabolism and synthesis of estrogens are considered to play very important roles in the pathogenesis and development of various sex steroid-dependent neoplasms including breast and endometrial carcinoma. 17 beta-Hydroxysteroid dehydrogenase (17 beta-HSD) isozymes catalyze the interconversion of estradiol (E(2)) and estrone (E(1)), and thereby serve to modulate the tissue levels of bioactive E(2). 17 beta-HSD type 1 primarily catalyzes the reduction of E(1) to E(2), whereas 17 beta-HSD type 2 primarily catalyzes the oxidation of E(2) to E(1). In the human breast and its disorders, 17 beta-HSD type 1 is expressed in proliferative diseases without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17 beta-HSD type 2 is not detected in any of the lesions. In addition, 17 beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E(1), produced as a result of in situ aromatization, to E(2), a biologically potent estrogen, and exerts estrogenic actions on tumor cells through the estrogen receptor. On the other hand, in the human endometrium, 17 beta-HSD type 2 is expressed, but not 17 beta-HSD type 1. 17 beta-HSD type 2 is expressed in the secretory phase but not in any proliferative phase in the endometrial mucosa. The enzyme is expressed in 75% of endometrial hyperplasias and 37% of carcinoma cases. In endometrial carcinoma cases, a significant inverse correlation has been detected between 17 beta-HSD type 2 immunoreactivity and age (p < 0.02). These results indicate that oxidation of E(2) to E(1) is dominant in endometrial carcinoma, 17 beta-HSD types 1 and 2 play an important role in the regulation of in situ estrogen production in breast and endometrial carcinoma.

• Authors: H Sasano, T Suzuki, J Takeyama, H Utsunomiya, K Ito, N Ariga, T Moriya
• Journal: Oncology (Oncology) Vol. 59 Suppl 1 Pg. 5-12 ( 2000) ISSN: 0030-2414 [Print] Switzerland
• PMID: 11096350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright 2000 S. Karger AG, Basel

Chemical References

• Estradiol Dehydrogenases

Topics

• Blotting, Northern
• Breast Neoplasms (drug therapy, pathology)
• Endometrial Neoplasms (drug therapy, pathology)
• Estradiol Dehydrogenases (therapeutic use)
• Female
• Humans
• Immunohistochemistry