Pyk2/ERK 1/2 mediate Sp1- and c-Myc-dependent induction of telomerase activity by epidermal growth factor.
Epidermal growth factor (EGF) promotes growth of normal ovarian surface as well as malignant ovarian epithelial cells. Further, EGF receptors are present on both normal and malignant ovarian surface epithelial cells and they are often constitutively activated in many cancers. Since telomerase confers cellular immortalization and survival through increased cellular proliferation, we sought to investigate the potential role of EGF to regulate telomerase activity in normal and ovarian cancer cells. While exogenous EGF failed to activate telomerase in normal ovarian surface epithelial cells, in cancer cells we herein report that: exogenous EGF activates telomerase activity and human telomerase reverse transcriptase gene (hTERT) transcription; EGF-induced telomerase activity is ERK 1/2-dependent; EGF targets Sp1 and c-Myc binding sites within the core region of the hTERT promoter; and proline-rich tyrosine kinase 2 (Pyk2) is a key mediator of EGF-mediated telomerase activity. Together, these data show that dysregulation of EGF signaling may promote cancer cell survival through up-regulation of telomerase activity.
Bermudez
Yira
Y
Department of Pathology and Cell Biology, University of South Florida, Tampa, Florida 33612, USA.
Yang
Hua
H
Cheng
Jin Q
JQ
Kruk
Patricia A
PA
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism*; D005260:Female; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*
D016271:Proto-Oncogene Proteins c-myc; D016329:Sp1 Transcription Factor; D004815:Epidermal Growth Factor; D051418:Focal Adhesion Kinase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019098:Telomerase