Recent studies point to a close connection between cancer and ageing. Cellular senescence when initiated early in cancerous cells results in growth suppression due to permanent growth arrest. Sirtuins, belonging to family of the NAD-dependent deacetylases, play a crucial role in cellular metabolism and organismal ageing/ longevity. However, the role of human Sirtuin isoforms in malignancies and cellular senescence is still not clearly discernible. The present study is therefore designed to evaluate the correlation of SIRT1 expression with proliferation marker Ki-67, and growth arrest/senescence marker p27, during cervical cancer progression. The expression was evaluated by immunohistochemistry in 70 formalin fixed archival human cervical samples: normal/ASCUS (N= 20), squamous intraepithelial lesions (SIL N=20) and invasive squamous cell carcinoma (SCC, N= 30 samples). All the intraepithelial lesions and SCC cases were positive for human papilloma virus as detected by in-situ hybridization. The SIRT1 expression was either absent or feeble in cytoplasm of normal/ASCUS cervical epithelium, while a progressive increase in its expression was noted in 65% of preneoplastic lesions (SIL). Intriguingly, the invasive carcinoma showed heterogeneous pattern for both expression and localization of SIRT1: ranging from negative to strong expression levels and mixed localization pattern in cytoplasm only or both in nucleus and cytoplasm. The growth arrest/senescence marker p27 showed elevated level of expression in SIL cases compared to SCC (75%). Interestingly, the increased nucleo-cytoplasmic expression pattern of SIRT1 correlated well with the increased expression of p27 in the intraepithelial preneoplastic lesion. In conclusion, our results suggest activation of growth suppressive pathways by SIRT1-p27 regulation, atleast in the in preneoplastic lesions of cancer cervix which may help retard its progression to invasive cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3951. doi:1538-7445.AM2012-3951

©2012 American Association for Cancer Research
2012