5alpha-reductases in human breast carcinoma: possible modulator of in situ androgenic actions.
The expression of 5alpha-reductase types 1 and 2 was examined in human breast carcinoma using immunohistochemistry and RT-PCR. Immunoreactivity for 5alpha-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 5alpha-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 5alpha-reductase type 1 immunoreactivity and androgen and progesterone receptor A or B labeling indexes, and immunoreactivities of 5alpha-reductase type 2, 17beta-hydroxysteroid dehydrogenase type 5, or 3beta-hydroxysteroid dehydrogenase, which recognizes both types I and II. An inverse correlation was detected between 5alpha-reductase type 1 immunoreactivity and tumor size, histological grade, or Ki-67 labeling index. 5alpha-Reductase type 2 immunoreactivity was significantly correlated with 17beta-hydroxysteroid dehydrogenase type 5 immunoreactivity, but not with other parameters. This study suggests that 5alpha-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, 5alpha-dihydrotestosterone, including inhibition of cancer cell proliferation, in hormone-dependent human breast carcinoma.
Suzuki
T
T
Department of Pathology, Tohoku University School of Medicine, Tohoku University Hospital (N.A., T.M.), Sendai 980-8575, Japan. t-suzuki@patholo2.med.tohoku.ac.jp
Darnel
A D
AD
Akahira
J I
JI
Ariga
N
N
Ogawa
S
S
Kaneko
C
C
Takeyama
J
J
Moriya
T
T
Sasano
H
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology; D013196:Dihydrotestosterone / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011944:Receptors, Androgen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007527:Isoenzymes; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase