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Research Paper
The BRK Tyrosine Kinase is Expressed in High-Grade Serous Carcinoma of the Ovary
Rosemarie E. Schmandt, Marsha Bennett, Stephanie Clifford, Angela Thornton, Feng Jiang, Russell R. Broaddus, Charlotte C. Sun, Karen H. Lu, Anil K. Sood and David Gershenson
volume 5 | issue 9
september 2006Pages: 1136 - 1141
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Background: We identified the BRK tyrosine kinase in a PCR-based screen of tyrosine kinases expressed by ovarian tumors. BRK expression is restricted to normal differentiating epithelial cells and its overexpression may play a role in processes related to tumor development and growth. Its expression in normal ovary and ovarian tumors has not previously been described, and is the focus of this study.
Methods: BRK expression levels were determined in 14 normal ovaries and 138 high-grade, late stage serous carcinomas of the ovary by immunohistochemical analysis, and in 19 ovarian cancer cell lines and immortalized ovarian surface epithelium by western blot analysis. Furthermore, BRK/PTK6 gene copy number was determined in 7 primary serous carcinomas by fluorescence in situ hybridization.
Results: Immunohistochemical studies indicate that BRK is highly expressed in 97/138 (70%) of high-grade, serous carcinomas of the ovary, but is absent in normal ovarian surface epithelia. BRK is also expressed by 9/19 of ovarian cancer cell lines, but is undetectable in immortalized ovarian surface epithelium. Interestingly, the BRK gene has been mapped to chromosome 20q13.3, a site frequently amplified in ovarian cancers, and associated with poor prognosis. We have determined by fluorescence in situ hybridization (FISH) that BRK is specifically amplified at low levels in 6/7 primary ovarian carcinomas.
Conclusions: The amplification of the BRK gene and over-expression of BRK protein in the majority of high-grade serous carcinomas and ovarian cancer cell lines suggest that BRK may play a role in the development and growth of ovarian tumors.
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 PDFIf 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.