eIF4E is a critical regulator of human papillomavirus (HPV)-immortalized cervical epithelial (H8) cell growth induced by nicotine.

eIF4E is a critical regulator of human papillomavirus (HPV)-immortalized cervical epithelial (H8) cell growth induced by nicotine. Toxicology. 2019 Mar 02;: Authors: Chen L, Wang H Abstract Tobacco smoke is known as a cofactor in the development of cervical precancer and cancer caused by human papillomavirus (HPV). The main component in cigarette smoke, nicotine, can be concentrated more strongly in cervical mucus than in blood and it has been implicated as a cocarcinogen that promotes a serial of cancers development through multiple prosurvival pathways. Although the mechanisms of nicotine-induced cell proliferation have been well studied in some epithelial cells, the molecular mechanism of its action in cervical epithelial cells is still unclear. The aims of this study were to investigate the detailed mechanism by which nicotine could induce cervical cancer growth. We found that nicotine simultaneously activates AKT/mTOR pathway in HPV-immortalized cervical epithelial (H8) cell line, followed by elevation of 4EBP1/eIF4E axis expression and its translational activity with dose-dependent and time-dependent manners. Besides, nicotine decreases eIF4E-4EBP1 binding activity in H8 cell line, which is associated with increased expression of phospho-4EBP1 at threonine 70. We therefore chose to evaluate whether this effect on eIF4E was involved in nicotine-induced proliferation. Remarkably, eIF4E knockdown by small interfering RNA diminishe...
Source: Toxicology - Category: Toxicology Authors: Tags: Toxicology Source Type: research