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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.

SUBMITTER: Miah S

PROVIDER: S-EPMC3412638 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Constitutive activation of breast tumor kinase accelerates cell migration and tumor growth in vivo.

Miah S S Martin A A Lukong K E KE

Oncogenesis 20120507

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 ...[more]

PMID: 23552639

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