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The Intracellular Tyrosine Kinase Brk Sensitizes Nontransformed Cells to Inducers of Apoptosis
Andrea Haegebarth, Rafael Nunez and Angela L. Tyner
volume 4 | issue 9
September 2005Pages: 1239 - 1246
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The intracellular tyrosine kinase Brk is expressed in regenerating epithelial tissues with highest levels in the gastrointestinal tract and skin. In these tissues, Brk is restricted to epithelial cells that are exiting the cell cycle and undergoing terminal differentiation. While not expressed in mammary gland, Brk expression is often induced in primary breast tumors and breast tumor cell lines. To identify potential oncogenic functions of Brk, we utilized the immortalized Rat1a rat fibroblast cell line that is highly sensitive to transformation. We generated Rat1a cell lines that stably overexpress wild-type and activated Brk, and we analyzed their growth properties and ability to undergo apoptosis in response to stress and DNA damage. Overexpression of Brk did not induce anchorage-independent growth, and no changes in cell morphology or cell cycle progression were observed. However, when constitutively expressed, Brk sensitized Rat1a cells to a variety of apoptotic stimuli including serum deprivation and a combination of UV irradiation and serum starvation. These findings indicate that Brk does not promote proliferation of nontransformed cells, but plays a positive role in the regulation of the apoptotic response to DNA-damage and stress.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.