It is well known that sex
steroids are involved in the growth of breast
cancers, and the great majority of
breast carcinomas express
estrogen (ER),
progesterone (PR), and
androgen (AR) receptors. In particular, recent studies have demonstrated that
estrogens and
androgens are locally produced in
breast carcinoma tissues, and total blockade of in situ
estrogen production potentially leads to an improvement in prognosis of
breast cancer patients. Therefore, it is important to obtain a better understanding of sex
steroid-producing
enzymes in
breast carcinoma tissues. In this review, we summarize recent studies on the expression and regulation of
enzymes related to intratumoral production of
estrogens (
aromatase, 17beta-
hydroxysteroid dehydrogenase type 1 (17betaHSD1), and
steroid sulfatase (STS) etc) and
androgens (17betaHSD5 and 5alpha-
reductase) in human
breast carcinoma tissues, and discuss the
biological and/or clinical significance of these
enzymes. The cellular localization of
aromatase in
breast carcinoma tissues still remains controversial. Therefore, we examined localization of
aromatase mRNA in
breast carcinoma tissues by
laser capture microdissection/real time-polymerase chain reaction.
Aromatase mRNA expression was detected in both
carcinoma and intratumoral stromal cells, and the expression level of
aromatase mRNA was higher in intratumoral stromal cells than in
carcinoma cells in the cases examined. We also examined an association among the immunoreactivity of
enzymes related to intratumoral
estrogen production and ERs in
breast carcinoma tissues, but no significant association was detected. Therefore, the
enzymes responsible for the intratumoral production of
estrogen may not always be the same among
breast cancer patients, and not only
aromatase but also other
enzymes such as STS and 17betaHSD1 may have important therapeutic potential as targets for endocrine
therapy in
breast cancer patients.