Aromatase in human breast carcinoma as a key regulator of intratumoral sex steroid concentrations.
It is well-known that estrogens are closely involved in the growth of human breast carcinomas, and that the great majority of breast carcinoma express estrogen receptors. Recent studies have demonstrated that estrogens are locally produced and act on the breast carcinoma tissue. Among these pathways, aromatase is a key enzyme for intratumoral production of estrogens in breast carcinomas, and aromatase inhibitors are currently used in the breast carcinoma in postmenopausal women as an estrogen deprivation therapy. This review summarizes the results of recent studies on the expression and regulation of aromatase in breast carcinoma tissues, and discusses the potential biological and/or clinical significance of aromatase. Aromatase is abundantly expressed in various cell types, such as carcinoma cells, intratumoral stromal cells, and adipocytes adjacent to the carcinoma, in breast carcinoma tissues. Further, a key regulator for aromatase expression differed according to cell type. In addition, aromatase suppressed in situ production of bioactive androgen, 5alpha-dihydrotestosterone (DHT), in breast carcinoma. Aromatase inhibitors may thus have additional antiproliferative effects through increasing local DHT concentration with estrogen deprivation.
Suzuki
Takashi
T
Department of Pathology, Tohoku University School of Health Sciences, Sendai, Japan.
Miki
Yasuhiro
Y
Akahira
Jun-Ichi
J
Moriya
Takuya
T
Ohuchi
Noriaki
N
Sasano
Hironobu
H
D001141:Aromatase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004967:Estrogens / Q000172:deficiency; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D012739:Gonadal Steroid Hormones / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009376:Neoplasms, Hormone-Dependent / Q000628:therapy; D009994:Osmolar Concentration; D014018:Tissue Distribution
D004967:Estrogens; D012739:Gonadal Steroid Hormones; D001141:Aromatase