STEAP1 is over-expressed in breast cancer and down-regulated by 17beta-estradiol in MCF-7 cells and in the rat mammary gland.
Six transmembrane epithelial antigen of the prostate 1 (STEAP1) was identified as a prostate-specific cell-surface antigen over-expressed in prostate cancer, and in human cancer cell lines obtained from several other tissues. Its cell surface location in all tumor types analyzed so far, and its absence in most vital organs in humans, turned STEAP1 into a potential target for anti-tumor immunotherapy. This study provides experimental evidence that STEAP1 is also over-expressed in human breast cancer cases, and in normal breast tissue adjacent to breast tumors, where it is localized in the cell membrane of epithelial cells. It is also demonstrated that STEAP1 transcription correlates negatively with estrogen receptor (ER) immunoreactivity, and positively with tumor grading in breast cancer cases. As estrogens are involved in breast cancer onset and progression, the response of STEAP1 to 17beta-estradiol (E2) was investigated in the mammary gland of rats, and in the human breast cancer cell line, MCF-7. These experiments demonstrated that STEAP1 is down-regulated by E2 in both models. The mechanisms underlying the STEAP1 response to E2 in vitro were further investigated in MCF-7 cells, and the results obtained suggest an effect mediated by the membrane-bound ERalpha (mbERalpha).
Maia
Cláudio J B
CJ
Centre of Investigation in Health Sciences-CICS, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal.
Socorro
Sílvia
S
Schmitt
Fernando
F
Santos
Cecília R A
CR
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism / Q000502:physiology; D005260:Female; D018226:Fibroadenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism; D042361:Mammary Glands, Human / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D047628:Estrogen Receptor alpha; D009363:Neoplasm Proteins; C540293:STEAP1 protein, rat; D004958:Estradiol; D010088:Oxidoreductases; C432763:STEAP1 protein, human