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.

BCAR3, Cas, DNA synthesis, EGF, IGF-1, Insulin, Microinjection, SH2 domain, article, breast cancer antiestrogen resistance 3 protein, breast cell, cancer cell culture, cell cycle progression, cell strain MCF 12A, controlled study, epidermal growth factor, female, human, human cell, membrane protein, microinjection, mitogenesis, plasmid, priority journal, protein SH2, protein expression, protein function, signal transduction, small interfering RNA, unclassified drug
dx.doi.org/10.1016/j.bbrc.2008.08.040, hdl.handle.net/1765/15124
Biochemical and Biophysical Research Communications
Erasmus MC: University Medical Center Rotterdam

Oh, M.J, van Agthoven, A.J, Choi, J-E, Jeong, Y-J, Chung, J.H, Kim, C.M, & Jhun, B.H. (2008). BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells. Biochemical and Biophysical Research Communications, 375(3), 430–434. doi:10.1016/j.bbrc.2008.08.040