BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells

Biochem Biophys Res Commun. 2008 Oct 24;375(3):430-4. doi: 10.1016/j.bbrc.2008.08.040. Epub 2008 Aug 21.

Abstract

BCAR3 (breast cancer anti-estrogen resistance 3) is a signal transducer containing an SH2 domain, a proline/serine-rich domain and a GDP-exchange factor homologous domain, whose role in signaling pathways is currently unclear. Furthermore, BCAR3 is implicated in anti-estrogen resistance of breast cancer cells. In the present study, we investigated the functional role of BCAR3 in a mitogenic signaling pathway of EGF in non-tumorigenic human breast epithelial MCF-12A cells. Microinjection of an anti-BCAR3 antibody, siRNAs targeting BCAR3 and an SH2 domain of BCAR3 inhibited EGF-induced DNA synthesis. Direct association of BCAR3 with activated EGF receptor and Cas was observed. Lastly, microinjection of a BCAR3 expression plasmid induced DNA synthesis. These findings suggest that the BCAR3 protein, through its SH2 domain, is involved in the signaling pathways of EGF leading to cell cycle progression, and that BCAR3 itself is part of a mitogenic signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Antibodies / immunology
  • Breast / cytology*
  • Breast / drug effects
  • Breast / metabolism*
  • Cell Cycle*
  • Cell Line
  • DNA / biosynthesis*
  • DNA / drug effects
  • Epidermal Growth Factor / metabolism*
  • Epidermal Growth Factor / pharmacology
  • ErbB Receptors / metabolism
  • Guanine Nucleotide Exchange Factors
  • Humans
  • Microinjections
  • Mitosis
  • RNA, Small Interfering / genetics
  • src Homology Domains / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies
  • BCAR3 protein, human
  • Guanine Nucleotide Exchange Factors
  • RNA, Small Interfering
  • Epidermal Growth Factor
  • DNA
  • ErbB Receptors