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PROFILES OF GENE EXPRESSION ASSOCIATED WITH TETRACYCLINE OVER EXPRESSION OF HSP70 IN MCF-7 BREAST CANCER CELLS
Citation:
Hester, S D., J A. Barnes, E. Winkfield, AND J W. Allen. PROFILES OF GENE EXPRESSION ASSOCIATED WITH TETRACYCLINE OVER EXPRESSION OF HSP70 IN MCF-7 BREAST CANCER CELLS. Presented at American Association of Cancer Research, San Francisco, CA, April 6-10, 2002.
Description:
Profiles of gene expression associated with tetracycline over expression of HSP70 in MCF-7 breast cancer cells.
Heat shock proteins (HSPs) protect cells from damage through their function as molecular chaperones. Some cancers reveal high levels of HSP70 expression in association with increased proliferation, resistance to therapy and poor disease prognosis. We have recently developed an MCF- 7 breast cancer cell line with tetracycline regulation of HSP70 expression and demonstrated that overexpression of HSP70 is associated with faster cell cycling and increased thermotolerance. The present studies were aimed at identifying genes with altered expression levels that may be involved in these HSP70 induced effects. We used total RNA isolated from MCF- 7 cells with or without over- expressed HSP70 to perform differential microarray analysis in a 2-dye experiment using a custom human IOK cDNA slide. We examined global differential gene expression, with a focus on functional categories that could account for the observed increased cell proliferation including oncogene, cell cycle, cytoskeleton, and apoptosis. Alterations in the expression of several genes were consistent with their functional activities involving growth ( PCNA, p2l , cyclin D I, insulin-like growth factor), apoptosis (Fas ligand, caspase I, apoptosis inhibitor I, caspase 8), signal transduction (yes-associated protein, transforming growth factor-beta, vascular endothelial growth factor), oncogene (c-myc binding protein, neuroblastoma ras, v-avian myc), and cytoskeleton (tropomyosin, microtubule-associated protein, tubulin). Genes with 3 fold increased expression in Hsp70 on versus off condition included v-ras oncogene, putative c-myc responsive, c-myc binding protein, eukaryotic translation elongation factor, alpha interferon and 2 ESTs
similar to ubiquitin conjugation. Overall, the comparison of gene expression profiles in MCF- 7 cells with elevated levels of HSP70 may provide additional information concerning the complex role of HSP70 in cells. Functional genomic approaches .comparing the gene expression patterns among cell lines with defined phenotypes may promote a better understanding of genes expressed by malignant cells which display an enhanced cell proliferation rate and may account for tumor progression.
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