Breast tumor-derived factors stimulate reduction of estrone to estradiol in nonmalignant breast tissue.
This study examines the paracrine influence by human breast carcinoma cells (UISO-BCA-1) on nonmalignant breast tissue in vitro. The 17 beta-OH-SDH-mediated reductive pathway (estrone-->estradiol) was significantly increased in nonmalignant breast tissue coincubated with human breast carcinoma cells, compared to control tissues incubated in the media alone. No influence on the enzyme activity was noticed in coincubated breast cancer cells. Preincubation of breast cancer cells with estradiol (10(-8) M) significantly decreased the enzyme activity in coincubated nonmalignant breast tissue, which was restored to control levels by addition of R5020 (10(-8) M), tamoxifen (10(-6) M), or a combination of both. In nonmalignant tissues incubated in the presence of growth factor TGF alpha, enzyme activity was reduced to between 46% and 76%. No other growth factors (IGF I, IGF II, PDGF) influenced enzyme activity. In nonmalignant tissues incubated with malignant tumor cytosol, enzyme activity was increased in 16% cases, inhibited in 21%, and not significantly changed in 63%. The data from the present study suggest that factors produced by breast carcinoma cells may influence interconversion of estradiol in nonmalignant tissue. In patients, factors produced by malignant tumor mass may have paracrine influence on surrounding nonmalignant breast tissue and, thereby, may influence the estrogen availability to tumor mass.
Mehta
R R
RR
Specialized Center for Cancer Research and Education, University of Illinois Medical Center, Cook County Hospital, Chicago.
Graves
J M
JM
D015067:17-Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000378:metabolism*; D001940:Breast / Q000201:enzymology*; D001943:Breast Neoplasms / Q000201:enzymology*; D002277:Carcinoma / Q000201:enzymology*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D011372:Progestins / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D011372:Progestins; D013629:Tamoxifen; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases