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COMPARATIVE MICROARRAY EXPRESSION ANALYSIS OF SELECTED CANCER RELEVANT GENES IN HYPERTENSIVE RESISTANT VERSUS SUSCEPTIBLE RODENT STRAINS
Citation:
HEIDENFELDER, B., J. E. GALLAGHER, D. REIF, E. HUBAL, J. R. BRAMBLE, AND J. HARKEMA. COMPARATIVE MICROARRAY EXPRESSION ANALYSIS OF SELECTED CANCER RELEVANT GENES IN HYPERTENSIVE RESISTANT VERSUS SUSCEPTIBLE RODENT STRAINS. Presented at American Association for Cancer Research, Los Angeles, CA, April 14 - 18, 2007.
Description:
Hypertension and cancer are prevalent diseases. Epidemiological studies suggest that hypertension may increase the long term risk of cancer. Identification of resistance and/or susceptibility genes using rodent models could provide important insights into the management and treatment of hypertension and cancer. Gene expression analysis was performed on lung RNA isolated from two rat strains: hypertension-resistant Wistar Kyoto (WKY) and spontaneously hypertensive (SHR). RNA was hybridized to Affymetrix R230 2.0 rat whole genome chips. Data reported here are restricted to expression analysis for cancer-relevant genes showing differential expression (fold change >1.5 and false discovery rate <0.05) in the SHR versus WKY strains. Relative to the parent WKY strain, SHR rats showed expression decreases in several genes involved in the regulation of cell death and DNA repair. The rat homolog of human repressor activator protein (hRap1), which is necessary for proper telomere length maintenance, was downregulated 5.7 fold in SHR. X-ray repair cross complementation (Ku80 or xrcc5), a regulatory target of hRap1 involved in DNA repair, was downregulated 2.5 fold in SHR. Granzyme B, with pro-apoptotic and antitumor functions, is downregulated 2.3-fold in SHR, along with perforin, Stat3, and haptoglobin (downregulated 1.8, 3.1, and 1.7 fold, respectively)¿all of which are upstream members of the same lytic pathway. Meanwhile, ubiquitin fusion cleavage factor 2 (UFD2), which is cleaved by granzyme B during apoptosis, is upregulated 1.6 fold relative to WKY rats, pointing to a reduction of normal apoptotic activity in hypertensive strains. Our results showing alterations in expression of genes relevant to apoptosis and DNA repair employing hypertension resistant versus susceptible rodent strains will help to elucidate possible shared biological pathways operative in hypertensive and malignant processes. (These findings do not necessarily represent EPA policy)