Abstract
Telomerase is an enzyme that can extend the ends of chromosomes and is aberrantly expressed in 90% of all cancers. Recent findings suggest that telomerase has cellular functions independent of its catalytic ability to elongate the telomere. Telomerase expression has been implicated in aiding cellular response to double strand breaks in DNA, to mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, can specifically enhance cell viability in response to the hypoxic microenvironment of a tumor. Telomerase expression is upregulated by the kinase Akt, which is induced by the neuregulin/ErbB signaling pathway. Neuregulin is a glycoprotein that is necessary for smooth muscle and neuronal development. Neuregulin activates the ErbB tyrosine kinase family, which promotes cell survival, proliferation, and differentiation. Recently, neuregulin has been shown to be upregulated in response to severe hypoxia, and may reduce the inflammation response to oxidative stress. The mechanism of neuregulin expression protection is unclear, though microarray data shows that neuregulin expression decreases the expression of several pro-inflammatory cytokines. We hypothesize that neuregulin can regulate the expression of telomerase during severe oxidative stress, and that telomerase expression promotes cell survival during hypoxia. We examined telomerase expression in differentiated rat neuroblastoma cell and observed a significant increase in telomerase expression in response to the addition of physiological levels of neuregulin. Surprisingly, treatment with the oxidizing agent diidopropyl flourosphophate (DFP) had no effect on telomerase expression in these cells. The neuregulin-mediated telomerase expression did confer a mild survival benefit in this cell line. These results could strengthen the link between neurodegeneration and cancer.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B51.
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