Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.
OBJECTIVE
Over-expression of epidermal growth factor-receptors (EGF-R) has been 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 nicotine-enhanced proliferation rates in two cervical cancer cell lines.


METHODS
We studied (a) nicotine-induced increase in the cellular expression of EGF-R in human papillomavirus (HPV)-positive ME-180 and HPV-negative HT-3 cervical cancer cell line cultures, using a semi-quantitative immunofluorescent 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 concentrations caused increased expression of EGF-R in both cervical cancer cell lines. Up-regulation of EGF-R was associated with increased cellular proliferation. Decreased expression of EGF-R was associated with decreased cellular proliferation. These data were consistent with EGF-R expression as a mechanism 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.
Mathur
R S
RS
Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston 29425, USA. mathurs@musc.edu
Mathur
S P
SP
Young
R C
RC
D002455:Cell Division; D004815:Epidermal Growth Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000187:drug effects*; D005260:Female; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
D004815:Epidermal Growth Factor; D009538:Nicotine; D066246:ErbB Receptors