1. Detection of chromosomal aberrations by comparative genomic hybridization during transformation of human breast epithelial cells in vitro.
- Author
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Balogh GA, Russo IH, Balsara BR, and Russo J
- Subjects
- Animals, Benzopyrenes toxicity, Breast drug effects, Breast Neoplasms chemically induced, Cell Line, Transformed, Cell Line, Tumor, Cell Transformation, Neoplastic chemically induced, Chromosomes, Human drug effects, Chromosomes, Human genetics, Cytogenetic Analysis, Epithelial Cells drug effects, Female, Genes, ras genetics, Humans, Mice, Mice, SCID, Nucleic Acid Hybridization, Breast Neoplasms genetics, Cell Transformation, Neoplastic genetics, Chromosome Aberrations chemically induced
- Abstract
Breast cancer is the most frequent malignancy in women. It is well recognized that tumorigenesis is a multistep process resulting from the accumulation of sequential genetic alterations. In breast cancers LOH has been described on one or both arms of multiple chromosomes. Comparative genomic hybridization (CGH) analysis was performed to identify chromosomal imbalances in the breast epithelial cells (HBEC). We have used a human in vitro-in vivo system in which the environmental carcinogen benz(a)pyrene (BP) and the c-Ha-ras oncogene were utilized for inducing in vitro transformation of HBEC. Immortal MCF-10F cells were treated with BP which resulted in the transformed cell line BP-1 that was further enhanced by transfection with the c-Ha-ras to generate the cell line BP-1-Tras. This cell line is tumorigenic when injected in severe combined immunodeficient (SCID) mice, generating the tumor cell line BP-1-Tras T J#4. Our comparative genomic hybridization analysis indicates that the most overrepresented segment after cell transformation and in the BP-1, BP-1-Tras and in the tumor cell line were 1p (80%), 5q21-ter (80%), 8q24.1 (90%) and Xq27-28 (60%). DNA sequence amplification at 10p14-15 was observed in BP-1-Tras T J#4 cells. Allelic losses of chromosome 4, 8p11-21 and 15q11-12, occur after cell transformation and are maintained consistently during tumorigenesis.
- Published
- 2006
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