Carcinogenesis, Vol. 21, No. 4, 769-776,
April 2000
© 2000 Oxford University Press
Carcinogenesis |
Establishment of a radiation- and estrogen-induced breast cancer model
Center for Radiological Research, VC11-218, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, New York, NY 10032, USA
It is well accepted that cancer arises in a multistep fashion in which exposure to environmental carcinogens is a major etiological factor. The aim of this work was to establish an experimental breast cancer model in order to understand the mechanism of neoplastic transformation induced by high LET radiation in the presence of 17ß-estradiol (E). Immortalized human breast cells (MCF-10F) were exposed to low doses of high LET 
particles (150 keV/µm) and subsequently cultured in the presence or absence of E for periods of up to 10 months post-irradiation. MCF-10F cells irradiated with either a single 60 cGy dose or 60/60 cGy doses of particles showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth and invasive capability before becoming tumorigenic in nude mice. In particle-irradiated cells and in those cells subsequently cultured in the presence of E, increased BRCA1, BRCA2 and RAD51 expression were detected by immunofluorescence staining and quantified by confocal microscopy. These studies showed that high LET radiation such as that emitted by radon progeny, in the presence of estrogen, induced a cascade of events indicative of cell transformation and tumorigenicity in human breast epithelial cells.
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