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Functional Characterization of Primary Mammary Cells With Life Span Extension Using Ectopic Telomerase
Annual rept. 1 Aug 2001-31 Jul 2002
VIRGINIA COMMONWEALTH UNIV RICHMOND
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In studies to define the changes in gene expression after expression of telomerase in normal human breast epithelial cells using microarray, we have focused on obtaining appropriate cell strains and lines for use with Affymetrix arrays in order to compare with spotted arrays from commercially available sources. Thus far, although still quite preliminary, our data indicate a relationship between the life span extended cells and the spontaneously immortal cells rather than those cells that are approaching senescence in terms of gene expression patterns. Interestingly, the telomerase-expressing normal mammary cells have similar expression patterns to the spontaneously immortal line for certain genes related to proliferation rather than specific markers related to a cancer-like phenotype. A direct comparison to normal young mammary strains is currently underway, with the hope of defining any differences in young diploid normal cells and those that have an extended life span using ectopic expression of human telomerase. Our hypothesis is that expression of telomerase prevents the genomic instability associated with the immortalization process, which would also prevent the change in gene expression patterns observed for the spontaneously immortal lines as well as those genes expressed as cells approach senescence.
APPROVED FOR PUBLIC RELEASE