Identification of a novel EGF-sensitive cell cycle checkpoint

Journal Article · Thu Feb 01 04:00:00 EST 2007 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2006.10.026· OSTI ID:20972111

Walker, Francesca ^[1]; Huihua, Zhang ^[1]; Burgess, Antony W ^[1]

---

1. Ludwig Institute for Cancer Research, P.O Royal Melbourne Hospital, Parkville, Victoria 3050 (Australia)

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.

• OSTI ID: 20972111
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 3 Vol. 313; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL CYCLE
DNA
GROWTH FACTORS
MITOSIS
NEOPLASMS
PHENOTYPE
RECEPTORS
TUMOR CELLS