Telomerase is aberrantly expressed in 90% of all cancers, and is well characterized for its ability to extend the ends of chromosomes, the telomere. Although telomerase expression is predominantly associated with its ability to extend telomeres, there have been recent findings that suggest that telomerase has multiple cellular functions independent of its catalytic ability, and some of those functions help promote cell survival in response to severe oxidative stress. To date, telomerase expression as been implicated in aiding a cell's response to double strand breaks in DNA, mitochondria dysfunction, inhibition of apoptosis, and the promotion of cell proliferation. The protein component of telomerase, TERT, is also 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 severe hypoxia, and may reduce the inflammation response to oxidative stress. The mechanism of neuregulin 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. Inducing oxidative stress and hypoxia in differentiated rat neuroblastoma cells caused significant increases in telomerase expression. 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.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3222.

©2010 American Association for Cancer Research
2010