Expression/localization patterns of sirtuins (SIRT1, SIRT2, and SIRT7) during progression of cervical cancer and effects of sirtuin inhibitors on growth of cervical cancer cells

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sapna SinghGayatri Ramakrishna

Abstract

Sirtuins belong to the family of class III histone deacetylases; its role in neoplasia is controversial as both tumor-suppressive and promoting functions have been reported. There are very few reports available, where expressions of sirtuin isoforms are comprehensively analyzed during neoplasia. Therefore, in the present study, the expression of SIRT1, SIRT2, and SIRT7 during different stages of cervical cancer progression was analyzed. The normal cervical epithelium showed feeble expression of sirtuin isoforms, SIRT1, SIRT2, and SIRT7. A significant increase in SIRT1 expression was noted in the cytoplasm as well as in the nucleus of proliferative layers of cervical epithelium in squamous intraepithelial lesions (SIL); however, in the squamous cell carcinomas (SCC), a heterogeneous pattern of SIRT1 expression varying from low to high was noted. A progressive increase in the expression of both SIRT2 and SIRT7 was noted during cancer progression in the following order: normal < preneoplasia < cancer. Cervical cancer cell lines, HeLa and SiHa, showed higher levels of SIRT1 and SIRT2 in comparison to the immortalized cell counterpart, HaCaT. Specific inhibitors of SIRT1 (Ex527) and SIRT2 (AGK2) impaired the growth of the cervical c...Continue Reading

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