Establishment of a radiation- and estrogen-induced breast cancer model

• Published in: Carcinogenesis (New York) Vol. 21; no. 4; pp. 769 - 776
• Main Authors: Calaf, Gloria M., Hei, Tom K.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.04.2000; Oxford Publishing Limited (England)
• Subjects: 17β-estradiol; Alpha Particles; Animals; Biological and medical sciences; Biological effects of radiation; bovine serum albumin; BRCA1 Protein - analysis; BRCA2 Protein; Breast Neoplasms - etiology; BSA; Carcinogenesis, carcinogens and anticarcinogens; Cell Transformation, Neoplastic; Chemical agents; DMEM; Dulbecco's modified Eagle's medium; Estradiol - toxicity; Female; Fundamental and applied biological sciences. Psychology; Humans; Ionizing radiations; LET; Linear Energy Transfer; Medical sciences; Mice; Mice, SCID; Neoplasm Proteins - analysis; Neoplasms, Radiation-Induced - etiology; PBS; phosphate-buffered saline; Tissues, organs and organisms biophysics; Transcription Factors - analysis; Tumor Cells, Cultured; Tumors; Human; Alpha irradiation; Toxicity; 17β-Estradiol; Malignant tumor; Gene expression; Cell transformation; Carcinogenesis; In vitro; Mammary gland diseases; Carcinogen; Established cell line; Epithelial cell; Biological effect; Mammary gland; Tumor suppressor gene
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/21.4.769

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 17β-estradiol (E). Immortalized human breast cells (MCF-10F) were exposed to low doses of high LET α 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 α 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 α 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.