Abstract
Overcoming cancer health disparities is one of the best opportunities available for lessening the burden of cancer. Telomerase is an enzyme predominantly associated with its ability to extend the ends of chromosomes, or telomeres, and is expressed in 90% of all cancers. Recent findings suggest that telomerase has multiple cellular functions completely independent of its catalytic ability. Some of these functions help promote cell survival in response to severe oxidative stress which in turn should aid in the ongoing battle against cancer health disparities. Telomerase expression has been implicated in aiding a cell's response to double strand strand breaks in DNA, mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, is thought to specifically enhance cell viability in response to the hypoxic microenvironment of a tumor. These protective roles of TERT could be vital in promoting cell survival during severe hypoxia. Telomerase expression is upregulated by the kinase Akt, which is in turn 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 serve 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. Based on these facts, our hypothesis states that neuregulin can regulate the expression of telomerase during severe oxidative stress, and that telomerase expression promotes cell survival during hypoxia. The addition of physiologic levels of neuregulin was able to induce telomerase expression, indicating that telomerase activation could play an important role in the cellular response to oxidative stress.
Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):B50.
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