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Title: Identification of a novel EGF-sensitive cell cycle checkpoint

Abstract

The site of action of growth factors on mammalian cell cycle has been assigned to the boundary between the G1 and S phases. We show here that Epidermal Growth Factor (EGF) is also required for mitosis. BaF/3 cells expressing the EGFR (BaF/wtEGFR) synthesize DNA in response to EGF, but arrest in S-phase. We have generated a cell line (BaF/ERX) with defective downregulation of the EGFR and sustained activation of EGFR signalling pathways: these cells undergo mitosis in an EGF-dependent manner. The transit of BaF/ERX cells through G2/M strictly requires activation of EGFR and is abolished by AG1478. This phenotype is mimicked by co-expression of ErbB2 in BaF/wtEGFR cells, and abolished by inhibition of the EGFR kinase, suggesting that sustained signalling of the EGFR, through impaired downregulation of the EGFR or heterodimerization, is required for completion of the cycle. We have confirmed the role of EGFR signalling in the G2/M phase of the cell cycle using a human tumor cell line which overexpresses the EGFR and is dependent on EGFR signalling for growth. These findings unmask an EGF-sensitive checkpoint, helping to understand the link between sustained EGFR signalling, proliferation and the acquisition of a radioresistant phenotype in cancer cells.

Authors:
 [1];  [2];  [2]
  1. Ludwig Institute for Cancer Research, P.O Royal Melbourne Hospital, Parkville, Victoria 3050 (Australia). E-mail: francesca.walker@ludwig.edu.au
  2. Ludwig Institute for Cancer Research, P.O Royal Melbourne Hospital, Parkville, Victoria 3050 (Australia)
Publication Date:
OSTI Identifier:
20972111
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 3; Other Information: DOI: 10.1016/j.yexcr.2006.10.026; PII: S0014-4827(06)00452-6; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CELL CYCLE; DNA; GROWTH FACTORS; MITOSIS; NEOPLASMS; PHENOTYPE; RECEPTORS; TUMOR CELLS

Citation Formats

Walker, Francesca, Zhang Huihua, and Burgess, Antony W. Identification of a novel EGF-sensitive cell cycle checkpoint. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2006.10.026.
Walker, Francesca, Zhang Huihua, & Burgess, Antony W. Identification of a novel EGF-sensitive cell cycle checkpoint. United States. doi:10.1016/j.yexcr.2006.10.026.
Walker, Francesca, Zhang Huihua, and Burgess, Antony W. Thu . "Identification of a novel EGF-sensitive cell cycle checkpoint". United States. doi:10.1016/j.yexcr.2006.10.026.
@article{osti_20972111,
title = {Identification of a novel EGF-sensitive cell cycle checkpoint},
author = {Walker, Francesca and Zhang Huihua and Burgess, Antony W.},
abstractNote = {The site of action of growth factors on mammalian cell cycle has been assigned to the boundary between the G1 and S phases. We show here that Epidermal Growth Factor (EGF) is also required for mitosis. BaF/3 cells expressing the EGFR (BaF/wtEGFR) synthesize DNA in response to EGF, but arrest in S-phase. We have generated a cell line (BaF/ERX) with defective downregulation of the EGFR and sustained activation of EGFR signalling pathways: these cells undergo mitosis in an EGF-dependent manner. The transit of BaF/ERX cells through G2/M strictly requires activation of EGFR and is abolished by AG1478. This phenotype is mimicked by co-expression of ErbB2 in BaF/wtEGFR cells, and abolished by inhibition of the EGFR kinase, suggesting that sustained signalling of the EGFR, through impaired downregulation of the EGFR or heterodimerization, is required for completion of the cycle. We have confirmed the role of EGFR signalling in the G2/M phase of the cell cycle using a human tumor cell line which overexpresses the EGFR and is dependent on EGFR signalling for growth. These findings unmask an EGF-sensitive checkpoint, helping to understand the link between sustained EGFR signalling, proliferation and the acquisition of a radioresistant phenotype in cancer cells.},
doi = {10.1016/j.yexcr.2006.10.026},
journal = {Experimental Cell Research},
number = 3,
volume = 313,
place = {United States},
year = {Thu Feb 01 00:00:00 EST 2007},
month = {Thu Feb 01 00:00:00 EST 2007}
}