title: Up-regulation of epidermal growth factor-receptors (EGF-R) by nicotine in cervical cancer cell lines: this effect may be mediated by EGF.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston 29425, USA. mathurs@musc.edu
authors.forename: R S
authors.initials: RS
authors.lastname: Mathur
authors.forename: S P
authors.initials: SP
authors.lastname: Mathur
authors.forename: R C
authors.initials: RC
authors.lastname: Young
mesh_terms: 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
chemical_list: D004815:Epidermal Growth Factor; D009538:Nicotine; D066246:ErbB Receptors