17beta-hydroxysteroid dehydrogenases in human breast cancer.
Estrogen plays a pivotal role in development and progression of human breast carcinoma. Before menopause the main source of estrogen in women is circulating estrogen secreted from the ovary, but following menopause the source changes to the hormone that is converted from circulating adrenal androgens in peripheral tissues. Therefore, adrenal androgens have to be converted to estrogen to stimulate breast carcinoma cells. In these steps, several enzymes such as aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) are involved in the production of estrogens. The reaction related to 17beta-HSDs activity is one of the last steps of estradiol biosynthesis, and 14 isozymes of 17beta-HSD have been identified at this juncture. The balance of the relative expression levels of 17beta-HSD isozymes in human breast carcinomas is thought to play a pivotal role in supply of estradiol to estrogen receptor positive carcinoma cells. Understanding the character of 17beta-HSD isozymes in human breast carcinoma thus provides important information on the mechanisms of biosynthesis of estradiol in breast carcinoma and for development of a therapeutic agent targeted for inhibition of local estradiol synthesis in breast carcinoma cells. In the present review we summarize the roles played by 17beta-HSDs in human breast carcinoma to obtain a better understanding of the properties of 17beta-HSDs in human breast carcinoma.
Nagasaki
Shuji
S
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Miki
Yasuhiro
Y
Akahira
Jun-ichi
J
Suzuki
Takashi
T
Sasano
Hironobu
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology*; D006801:Humans
D015067:17-Hydroxysteroid Dehydrogenases