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 specificities, including estrone sulfate. Using a 2.4 kb cDNA clone, expression of human STS was undetectable by Northern hybridization, but STS RNA was detected in human placenta, human breast cancer samples, and in breast carcinoma cell lines following reverse transcriptase-PCR amplification, using specific primers to yield a product of 472 bp. In preliminary studies, stimulation of MCF-7 cell lines with estradiol (10(-8) M) resulted in an increased level of amplifiable STS RNA, and this upregulation of STS RNA could be abolished by tamoxifen. The estrone sulfatase activity in mammary tumors derived from N-nitrosomethylurea (NMU) treated rats was significantly decreased in animals treated with tamoxifen compared to control animals, regardless of the response of the tumors to the antiestrogen (P < 0.05). Although tamoxifen does not inhibit the estrone sulfatase enzyme in vitro, it may modulate the expression of STS RNA and the enzyme activity in vivo.
Evans
T R
TR
Department of Medical Oncology, St George's Hospital Medical School, London, England.
Rowlands
M G
MG
Luqmani
Y A
YA
Chander
S K
SK
Coombes
R C
RC
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001483:Base Sequence; D001706:Biopsy; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002273:Carcinogens; D017931:DNA Primers; D018076:DNA, Complementary; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology; D008770:Methylnitrosourea; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D017931:DNA Primers; D018076:DNA, Complementary; D012334:RNA, Neoplasm; D013629:Tamoxifen; D008770:Methylnitrosourea; D013429:Sulfatases; C020121:estrone sulfatase