{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:58:35Z","timestamp":1776211115786,"version":"3.50.1"},"reference-count":60,"publisher":"Portland Press Ltd.","issue":"1","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":1635,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:p>Re-expression of E2 in human papillomavirus (HPV) transformed tumour cells can induce apoptosis; however, some evidences also attribute an important role to E2 in sustaining tumorigenesis. In the present paper, we studied the effects of tumour necrosis factor (TNF)-\u03b1-mediated NF-\u03baB (nuclear factor kappa-light-chain-enhancer of activated B-cells) activation on E2-induced senescence in HPV16-integrated SiHa cells. The results show that E2 inhibits endogenous E6 gene expression and sensitizes SiHa cells to TNF-\u03b1-induced NF-\u03baB activation. Under this condition there was an increase in the expression of senescent proteins p53, p21, p27 and p16 and senescence-associated (SA)-\u03b2-galactosidase activity indicating that TNF-\u03b1 augments E2-mediated senescence. Re-expression of E2 expression with TNF-\u03b1 treatment resulted in an increase in the expression of anti-apoptotic Bcl2 (B-cell lymphoma 2) protein and other pro-survival genes like cyclin D1 (cyc D1), survivin and hTERT (human telomerase reverse transcriptase). Concomitantly, E2 + TNF-\u03b1 combination increased the survival of SiHa cells by positive changes in viability, proliferation and colony formation. E2-induced apoptotic tendency shifted towards senescence in presence of TNF-\u03b1 by arresting the cells at both G0\/G1 and G2\/M phases, thus enhancing cell survival. Another observation in the present study is the significant up-regulation of key senescence messaging factors regulated by NF-\u03baB namely interleukin (IL)-6, IL-8, high-mobility group protein A (HMGA)1 and B (HMGB)1 in E2-transfected cells treated with TNF-\u03b1. Our data provide a mechanistic basis and a new insight for the role of TNF-\u03b1 and E2 in linking cellular senescence, tumorigenesis and HPV re-infection.<\/jats:p>","DOI":"10.1042\/bsr20140160","type":"journal-article","created":{"date-parts":[[2015,1,12]],"date-time":"2015-01-12T10:27:25Z","timestamp":1421058445000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Re-expression of HPV16 E2 in SiHa (human cervical cancer) cells potentiates NF-\u03baB activation induced by TNF-\u03b1 concurrently increasing senescence and survival"],"prefix":"10.1042","volume":"35","author":[{"given":"Devan","family":"Prabhavathy","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandrasekaran\u00a0Karthik","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devarajan","family":"Karunagaran","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600 036, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2015,2,25]]},"reference":[{"key":"2021111618120948400_B1","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.humpath.2007.11.002","article-title":"Human papillomavirus: molecular and cytologic\/histologic aspects related to cervical intraepithelial neoplasia and carcinoma","volume":"39","author":"Thomison","year":"2008","journal-title":"Hum. 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