17Beta-estradiol is carcinogenic in human breast epithelial cells.
The association found between breast cancer development and prolonged exposure to estrogen suggests that this hormone is of etiologic importance in the causation of this disease. In order to prove this postulate, we treated the immortalized human breast epithelial cells (HBEC) MCF-10F with 17beta-estradiol (E(2)) for testing whether they express colony formation in agar methocel, or colony efficiency (CE), and loss of ductulogenesis in collagen matrix, phenotypes also induced by the carcinogen benz[a]pyrene (BP). MCF-10F cells were treated with 0.0, 0.007, 70nM, or 0.25mM of E(2) twice a week for 2 weeks. CE increased from 0 in controls to 6.1, 9.2, and 8.7 with increasing E(2) doses. Ductulogenesis was 75 +/- 4.9 in control cells; it decreased to 63.7 +/- 28.8, 41.3 +/- 12.4, and 17.8 +/- 5.0 in E(2)-treated cells, which also formed solid masses or spherical formations lined by a multilayer epithelium, whose numbers increased from 0 in controls to 18.5 +/- 6.7, 107 +/- 11.8 and 130 +/- 10.0 for each E(2) dose. MCF-10F cells were also treated with 3.7 microM of progesterone (P) and the CE was 3.39 +/- 4.05. At difference of E(2), P does not impaired the ductulogenic capacity. Genomic analysis revealed that E(2)-treated cells exhibited loss of heterozigosity in chromosome 11, as detected using the markers D11S29 and D11S912 mapped to 11q23.3 and 11q24.2-25, respectively These results also indicate that E(2), like the chemical carcinogen BP, induces in HBEC phenotypes indicative of neoplastic transformation.
Russo
Jose
J
Breast Cancer Research Laboratory, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. j.russo@fccc.edu
Lareef
M Hasan
MH
Tahin
Quivo
Q
Hu
Yun Fu
YF
Slater
Carolyn
C
Ao
Xiang
X
Russo
Irma H
IH
D001940:Breast / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002273:Carcinogens / Q000633:toxicity; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D004054:Diethylstilbestrol / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004958:Estradiol; D004054:Diethylstilbestrol