title: Epidermal growth factor-stimulated human cervical cancer cell growth             is associated with EGFR and cyclin D1 activation, independent of COX-2 expression             levels.
abstract: Cervical cancer constitutes the second most common cancer in women. It is             evident from earlier studies that epidermal growth factor (EGF) is a mitogen,             in that it mimics the function of estrogen by mediating cross-talk with other             oncoproteins. Although epidermal growth factor receptor (EGFR) is highly expressed             in breast and ovarian tumor tissues, its regulation by the exogenous source of             its ligand EGF in human papillomavirus (HPV)-associated cervical cancer remains             unclear. In this study, we addressed the question of whether EGF is required for             the proliferation of HPV-positive cervical cancer cells and what mechanisms are             involved. To determine this, we conducted a series of studies using HPV-positive             human cervical cancer cells, CaSki and HeLa, and stimulated the cells with EGF.             Our findings suggest that 6 h of stimulation with 10 ng/ml of EGF is sufficient             to induce cell cycle progression associated with a significant increase in DNA             synthesis, EGFR, COX-2 and cyclin D1 levels. Consistently, cellular localization             and Western blot analysis for p-EGFR (Try-1045) protein showed an increase after             EGF stimulation. Using siRNA gene knockdown assays we have shown that cyclin D1             siRNA has a significant negative effect on EGFR and inhibit cell growth independent             of COX-2 levels. In summary, our findings reveal that an exogenous EGF stimulation             may enhance HPV-related cervical cancer cell proliferation by activating EGFR             and cyclin D1 that is independent of COX-2 levels, suggesting that the inhibitors             of EGFR and cyclin D1 may be effective against cervical cancer cell proliferation.
authors.affiliation: New York University School of Medicine, Department of Environmental Medicine, Tuxedo, NY 10987, USA.
authors.forename: Rajkishen
authors.initials: R
authors.lastname: Narayanan
authors.forename: Hye Na
authors.initials: HN
authors.lastname: Kim
authors.forename: Narayanan K
authors.initials: NK
authors.lastname: Narayanan
authors.forename: Dominick
authors.initials: D
authors.lastname: Nargi
authors.forename: Bhagavathi
authors.initials: B
authors.lastname: Narayanan
mesh_terms: D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D052162:Human papillomavirus 16; D052161:Human papillomavirus 18; D006801:Humans; D058990:Molecular Targeted Therapy; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
chemical_list: C530104:CCND1 protein, human; D019938:Cyclin D1; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2; D066246:ErbB Receptors