Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16.
Summary of "Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16."
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.
Affiliation
Department of Biology, Clarkson University, Potsdam, NY 13699-5805, USA.
Journal Details
This article was published in the following journal.
Name: Virology
ISSN: 1096-0341
Pages: 19-27
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21982220
- DOI: http://dx.doi.org/10.1016/j.virol.2011.09.014
Medical and Biotech [MESH] Definitions
Receptor, Epidermal Growth Factor
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF related peptides including TRANSFORMING GROWTH FACTOR ALPHA, amphiregulin, and heparin-binding EGF-like growth factor. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Epidermal Growth Factor
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. EPIDERMAL GROWTH FACTOR exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells.
Receptor, Fibroblast Growth Factor, Type 2
A fibroblast growth factor receptor that is found in two isoforms. One receptor isoform is found in the MESENCHYME and is activated by FIBROBLAST GROWTH FACTOR 2. A second isoform of fibroblast growth factor receptor 2 is found mainly in EPITHELIAL CELLS and is activated by FIBROBLAST GROWTH FACTOR 7 and FIBROBLAST GROWTH FACTOR 10. Mutation of the gene for fibroblast growth factor receptor 2 can result in APERT SYNDROME.
Receptor, Erbb-3
A cell surface protein-tyrosine kinase receptor that is specific for NEUREGULINS. It has extensive homology to and can heterodimerize with the EGF Receptor (RECEPTOR, EPIDERMAL GROWTH FACTOR) and the erbB-2 receptor (RECEPTOR, ERBB-2). Overexpression of the erbB-3 receptor is associated with tumorigenesis.
Transforming Growth Factor Alpha
Factor isolated in a variety of tissues including epithelium, and maternal decidua. It is closely related to EPIDERMAL GROWTH FACTOR and binds to the EGF receptor. TGF-alpha acts synergistically with TGF-beta in inducing phenotypic transformation, but its physiological role is unknown.
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