Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: This effect may be mediated by EGF

PROBLEM: Over-expression of epidermal growth factor-receptors (EGF-R) has b een described in a variety of cancers, including cervical cancer. Nicotine may increase cellular proliferation rates through a mechanism involving EGF or EGF-R. In this study, we ascertain the effect of EGF antibodies on nico tine-enhanced proliferation rates in two cervical cancer cell lines. METHOD OF STUDY: We studied (a) nicotine-induced increase in the cellular e xpression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-ne gative HT-3 cervical cancer cell line cultures, using a semi-quantitative i mmunofluorescent antibody assay; (b) alterations in cellular proliferation in association with changes in EGF-R levels; and (c) the EGF-R mediation by EGF. RESULTS: Nicotine exposure at physiologically attainable plasma concentrati ons caused increased expression of EGF-R in both cervical cancer cell lines . Up-regulation of EGF-R was associated with increased cellular proliferati on. Decreased expression of EGF-R was associated with decreased cellular pr oliferation. These data were consistent with EGF-R expression as a mechanis m for the control of proliferation of the cervical cancer cells. The action of nicotine was abrogated when antibodies to EGF were added, implying that nicotine up-regulation of EGF-R may be mediated by EGF. CONCLUSIONS: Our data show that nicotine-induced proliferation of cervical cancer cells is mediated through EGF-R over-expression and that this action of nicotine utilizes EGF.