title: Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16.
abstract: The Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer.
authors: Department of Biology, Clarkson University, Potsdam, NY 13699-5805, USA. woodworth@clarkson.edu
authors: Craig D
authors: CD
authors: Woodworth
authors: Laura P
authors: LP
authors: Diefendorf
authors: David F
authors: DF
authors: Jette
authors: Abdulmajid
authors: A
authors: Mohammed
authors: Michael A
authors: MA
authors: Moses
authors: Sylvia A
authors: SA
authors: Searleman
authors: Dan A
authors: DA
authors: Stevens
authors: Katelynn M
authors: KM
authors: Wilton
authors: Sumona
authors: S
authors: Mondal
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002584:Cervix Uteri / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D052162:Human papillomavirus 16 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D030361:Papillomavirus Infections / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000821:virology
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012097:Repressor Proteins; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors