title: Constitutive activation of breast tumor kinase accelerates cell migration and tumor growth in vivo.
abstract: Breast tumor kinase (BRK) is a non-receptor tyrosine kinase overexpressed in most human breast tumors, including lymph node metastases, but undetected in normal mammary tissue or in fibroadenomas. The activity of BRK-like Src family tyrosine kinase, is regulated negatively by phosphorylation of C-terminal tyrosine 447. Although the kinase that regulates BRK activation has not been identified, we and others have previously shown that BRK-Y447F is a constitutively active variant. Because BRK-Y447F significantly enhances the catalytic activity of the enzyme, we investigated the role of the constitutively active BRK variant in tumor formation and metastasis. Using stable breast cancer cell MDA-MB-231 we observed significantly enhanced rates of cell proliferation, migration and tumor formation in BRK-Y447F stable cells compared with wild-type stable cell lines. Our results indicate full activation of BRK is an essential component in the tumorigenic role of BRK.
authors.affiliation: Department of Biochemistry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
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authors.initials: S
authors.lastname: Miah
authors.forename: A
authors.initials: A
authors.lastname: Martin
authors.forename: K E
authors.initials: KE
authors.lastname: Lukong
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