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-Reductases in Human Breast Carcinoma: Possible Modulator of in Situ Androgenic Actions1
Department of Pathology, Tohoku University School of Medicine (T.S., A.D.D., J.-I.A., S.O., C.K., J.T., H.S.), and Department of Pathology, Tohoku University Hospital (N.A., T.M.), Sendai 980-8575, Japan
Address all correspondence and requests for reprints to: Takashi Suzuki, M.D., Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. E-mail: t-suzuki{at}patholo2.med.tohoku.ac.jp
The expression of 5
-reductase types 1 and 2 was examined in human
breast carcinoma using immunohistochemistry and RT-PCR.
Immunoreactivity for 5
-reductase isozymes was also correlated with
various clinicopathological parameters to examine possible local
regulatory mechanisms of sex steroids, including progesterone and
androgens, in human breast carcinoma tissues. Immunoreactivity for
5
-reductase type 1 was detected in the cytoplasm and possibly in the
nuclear membrane of tumor cells in 35 of 60 invasive ductal carcinomas
(58%), and type 2 signal was detected in 9 of these 60 cases (15%).
The results from RT-PCR (n = 8) were consistent with those from
immunohistochemistry. A significant positive correlation was detected
between 5
-reductase type 1 immunoreactivity and androgen and
progesterone receptor A or B labeling indexes, and immunoreactivities
of 5
-reductase type 2, 17ß-hydroxysteroid dehydrogenase type 5, or
3ß-hydroxysteroid dehydrogenase, which recognizes both types I and
II. An inverse correlation was detected between 5
-reductase type 1
immunoreactivity and tumor size, histological grade, or Ki-67 labeling
index. 5
-Reductase type 2 immunoreactivity was significantly
correlated with 17ß-hydroxysteroid dehydrogenase type 5
immunoreactivity, but not with other parameters. This study suggests
that 5
-reductase type 1 is mainly expressed in human breast
carcinoma, which may play an important role in the in
situ production and actions of the potent androgen,
5
-dihydrotestosterone, including inhibition of cancer cell
proliferation, in hormone-dependent human breast carcinoma.
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