New developments in intracrinology of human breast cancer: estrogen sulfatase and sulfotransferase.
Steroid sulfatase (STS) hydrolyses biologically inactive estrogen sulfates to active estrogens, while estrogen sulfotransferase (EST) sulfonates estrogens to estrogen sulfates. Information regarding the expression of STS in human breast carcinoma tissues is still very limited compared to that of aromatase or 17beta-hydroxysteroid dehydrogenases (17beta-HSDs). In our study, EST and STS immunoreactivity was detected in carcinoma cells in 50 and 84 out of 113 breast carcinomas (44.2% and 74.3%, respectively), which was also associated with mRNA levels determined by RT/real-time PCR. Using microdissection/RT-PCR analyses, EST mRNA was localized to both carcinoma and intratumoral stromal cells, whereas STS was detected only in carcinoma or parenchymal cells. STS immunoreactivity was positively associated with tumor size. EST immunoreactivity was inversely correlated with tumor size or lymph node status and was significantly associated with a decreased risk of recurrence and improved prognosis. These data suggest that both EST and STS play important roles in the regulation of in situ estrogen production in human breast cancer. In addition, EST is an independent prognostic factor in human breast carcinoma and loss of EST may result in altered estrogen metabolism in hormone-dependent breast cancer cells. An inhibition of intratumoral STS in the patients with estrogen-dependent breast carcinoma is also considered to provide more clinical benefits, especially to the patients in which primary source of an availability of intratumoral estrogen is through STS rather than aromatase.
Sasano
Hironobu
H
Department of Pathology Tohoku University School of Medicine, Sendai, Japan. hsasano@patholo2.med.tohoku.ac.jp
Nagasaki
Shuji
S
Miki
Yasuhiro
Y
Suzuki
Takashi
T
D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D013429:Sulfatases; C039596:estrogen sulfatase