DETECTION OF BREAST CANCER-ASSOCIATED ESTRONE SULFATASE IN BREAST-CANCER BIOPSIES AND CELL-LINES USING POLYMERASE CHAIN-REACTION

Steroid sulfatase (STS) is a single enzyme with a range of substrate s pecificities, including estrone sulfate. Using a 2.4 kb cDNA clone, ex pression of human STS was undetectable by Northern hybridization, but STS RNA was detected in human placenta, human breast cancer samples, a nd in breast carcinoma cell lines following reverse transcriptase-PCR amplification, using specific primers to yield a product of 472 bp. In preliminary studies, stimuation of MCF-7 cell lines with estradiol (1 0(-8) M) resulted in an increased level of amplifiable STS RNA, and th is upregulation of STS RNA could be abolished by tamoxifen. The estron e sulfatase activity in mammary tumors derived from N-nitrosomethylure a (NMU) treated rats was significantly decreased in animals treated wi th tamoxifen compared to control animals, regardless of the response o f the tumors to the antiestrogen (P < 0.05). Although tamoxifen does n ot inhibit the estrone sulfatase enzyme in vitro, it may modulate the expression of STS RNA and the enzyme activity in vivo.