Endocrine characteristics of human breast epithelial cells, MCF-10F.
MCF-10F is a spontaneously immortalized nontransformed human breast epithelial cell line which does not grow in soft agar or form tumors in nude mice. Though the presence of estrogen receptors has not been found in these cells, they can metabolize estradiol very efficiently. The present study describes the endocrine characteristics of this cell line with respect to growth response to estradiol and its metabolites, estradiol metabolism and aromatase activity. MCF-10F cells were growth stimulated by 16alpha-hydroxyestrone and estriol, whereas, estradiol and other estradiol metabolites did not affect cell proliferation. The constitutive level of 16alpha-hydroxyestrone, a metabolite of estradiol biotransformation that has been associated with enhanced carcinogenesis in several animal, cell and tissue culture models, was a hundredfold higher in the non-transformed MCF-10F cells than in the transformed MCF-7 cells. Treatment with the carcinogen, dimethylbenz(a)anthracene (DMBA), however, did not upregulate 16alpha-hydroxylation as was observed in transformed MCF-7 cells. MCF-10F cells also had no detectable aromatase activity though the level of 17-oxidation was unusually high as compared with MCF-7 cells. Our results using the non-transformed MCF-10F cells as a model system suggests that the presence of high level of 16alpha-hydroxyestrone, a metabolite previously shown to be associated with malignant phenotype, may not be sufficient for breast cancer transformation.
Singhal
H
H
Division of Biochemical Endocrinology, Strang Cancer Research Laboratory, Rockefeller University, Smith Building, New York, N.Y., USA.
Guo
L
L
Bradlow
H L
HL
Mittelman
A
A
Tiwari
R K
RK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D065727:Cytochrome P-450 CYP2C8; D065729:Cytochrome P-450 CYP2C9; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004964:Estriol / Q000494:pharmacology; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000494:pharmacology; D039181:Steroid 16-alpha-Hydroxylase; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D006894:Hydroxyestrones; C026702:16-hydroxyestrone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001141:Aromatase; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D039181:Steroid 16-alpha-Hydroxylase; D004964:Estriol