Twenty years have passed since the non-
receptor tyrosine kinase,
Breast tumor kinase (BRK) was cloned. While BRK is evolutionarily related to the
Src family kinases it forms its own distinct sub-family referred here to as the BRK family
kinases. The detection of BRK in over 60% of
breast carcinomas two decades ago and more remarkably, its absence in the normal mammary gland attributed to its recognition as a mammary gland-specific potent oncogene and led BRK researchers on a wild chase to characterize the role of the
enzyme in
breast cancer. Where has this chase led us? An increasing number of studies have been focused on understanding the cellular roles of BRK in
breast carcinoma and normal tissues. A majority of such studies have proposed an oncogenic function of BRK in breast
cancers. Thus far, the vast evidence gathered highlights a regulatory role of BRK in critical cellular processes driving
tumor formation such as cell proliferation, migration and
metastasis. Functional characterization of BRK has identified several signaling
proteins that work in concert with the
enzyme to sustain such a malignant phenotype. As such targeting the non-
receptor tyrosine kinase has been proposed as an attractive approach towards therapeutic intervention. Yet much remains to be explored about (a) the discrepant expression levels of BRK in
cancer versus normal conditions, (b) the dependence on the enzymatic activity of BRK to promote
oncogenesis and (c) an understanding of the normal physiological roles of the
enzyme. This review outlines the advances made towards understanding the cellular and physiological roles of BRK, the mechanisms of action of the
protein and its therapeutic significance, in the context of
breast cancer.