Role of Src kinases in neu-induced tumorigenesis: Challenging the paradigm using Csk homologous kinase transgenic mice

Rafal Kaminski, Radoslaw Zagozdzon, Yigong Fu, Pawel Mroz, Wei Fu, Seyha Seng, Shalom Avraham, Hava Karsenty Avraham

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Amplification of the HER-2/neu (ErbB2) gene is observed in ∼30% of human breast cancers, correlating with a poor clinical prognosis. Src kinases are also involved in the etiology of breast cancer, and their activation was suggested to be necessary for Neu-induced oncogenesis. To address whether Src activity is essential for Neu-mediated tumorigenesis, we used a physiologic inhibitor of Src kinase activity, the Csk homologous kinase (CHK), expressed as a mammary tissue-specific transgene. Our data, using a physiologic inhibitor of Src activity (CHK), showed that blocking of Neu-induced Src activity without altering Src expression levels had no significant effects on Neu-mediated mammary tumorigenesis in vivo. This contradicts the current paradigm that activation of Src kinases is essential for Neu-induced oncogenesis. This study is the first to distinguish between the kinase-dependent and kinase-independent actions of Src and shows that its kinase-dependent properties are not requisite for Neu-induced tumorigenesis.

Original languageEnglish (US)
Pages (from-to)5757-5762
Number of pages6
JournalCancer Research
Volume66
Issue number11
DOIs
StatePublished - Jun 1 2006

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