BCAR3 regulates EGF-induced DNA synthesis in normal human breast MCF-12A cells.
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.
Oh
Myung-Ju
MJ
Department of Nanomedical Engineering, Pusan National University, Miryang, Geongnam 727-706, Republic of Korea.
van Agthoven
Ton
T
Choi
Ji-Eun
JE
Jeong
Yeon-Ji
YJ
Chung
Young-Hwa
YH
Kim
Cheol-Min
CM
Jhun
Byung H
BH
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology; D001940:Breast / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D008845:Microinjections; D008938:Mitosis; D034741:RNA, Small Interfering / Q000235:genetics; D018909:src Homology Domains / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; C118588:BCAR3 protein, human; D020662:Guanine Nucleotide Exchange Factors; D034741:RNA, Small Interfering; D004815:Epidermal Growth Factor; D004247:DNA; D066246:ErbB Receptors