comparison of gene expression profiles in chromate transformed beas-2b cells铬酸盐转化beas-2b细胞基因表达谱的比较.pdf

Comparison of Gene Expression Profiles in Chromate Transformed BEAS-2B Cells 1 1 1 2 1 Hong Sun , Harriet A. Clancy , Thomas Kluz , Jiri Zavadil , Max Costa * 1 Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, New York, United States of America, 2 Department of Pathology, NYU Cancer Institute and Center for Health Informatics and Bioinformatics, NYU Langone Medical Center, New York, New York, United States of America Abstract Background: Hexavalent chromium [Cr(VI)] is a potent human carcinogen. Occupational exposure has been associated with increased risk of respiratory cancer. Multiple mechanisms have been shown to contribute to Cr(VI) induced carcinogenesis, including DNA damage, genomic instability, and epigenetic modulation, however, the molecular mechanism and downstream genes mediating chromium’s carcinogenicity remain to be elucidated. Methods/Results: We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of Cr(VI) followed by anchorage-independent growth. These transformed cell lines not only exhibited consistent morphological changes but also acquired altered and distinct gene expression patterns compared with normal BEAS-2B cells and control cell lines (untreated) that arose spontaneously in soft agar. Interestingly, the gene expression profiles of six Cr(VI) transformed cell lines were remarkably similar to each other yet differed significantly from that of either control cell lines or normal BEAS-2B cells. A total of 409 differentially expressed genes were identified in Cr(VI) transformed cells compared to control cells. Genes related to cell-to-cell junction were upregulated