Brk is coamplified with ErbB2 to promote proliferation in breast cancer

Xiang, B., Chatti, K., Qiu, H., Lakshmi, B., Krasnitz, A., Hicks, J. B., Yu, M., Miller, W. T., Muthuswamy, S. K. (August 2008) Brk is coamplified with ErbB2 to promote proliferation in breast cancer. Proc Natl Acad Sci U S A, 105 (34). pp. 12463-8.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18719096
DOI: 10.1073/pnas.0805009105

Abstract

Amplification of the receptor tyrosine kinase ErbB2 is frequently observed in breast cancer. Amplification of erbB2 is also associated with multiple genomic gains and losses; however, the importance of these associated changes is largely unknown. We demonstrate that Brk, a cytoplasmic tyrosine kinase, is coamplified and coexpressed with ErbB2 in human breast cancers. ErbB2 interacts with Brk and increases its intrinsic kinase activity. Expression of Brk enhances the ErbB2-induced activation of Ras/MAPK signaling and cyclin E/cdk2 activity to induce cell proliferation of mammary 3-dimensional acini in culture. In a murine model of breast cancer, expression of Brk was found to shorten the latency of ErbB2-induced tumors by promoting cell proliferation, with no effect on protection from apoptosis. Furthermore, overexpression of Brk conferred resistance to the ability of Lapatinib, an ErbB2 kinase inhibitor, to inhibit ErbB2-induced proliferation. Thus, we identified Brk as a drug target for ErbB2-positive cancers.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > cancer > cancer types > breast cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
diseases & disorders > cancer > cancer types
CSHL Authors:
Communities: CSHL labs > Hicks lab
CSHL labs > Krasnitz lab
CSHL labs > Muthuswamy lab
Depositing User: Matt Covey
Date: 26 August 2008
Date Deposited: 28 Feb 2013 16:15
Last Modified: 08 Nov 2017 21:31
PMCID: PMC2527934
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27496

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