PMID- 16855388 OWN - NLM STAT- MEDLINE DCOM- 20070420 LR - 20200930 IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 5 IP - 9 DP - 2006 Sep TI - The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary. PG - 1136-41 AB - 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 seven 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 overexpression 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. FAU - Schmandt, Rosemarie E AU - Schmandt RE AD - Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1439, USA. rschmand@mdanderson.org FAU - Bennett, Marsha AU - Bennett M FAU - Clifford, Stephanie AU - Clifford S FAU - Thornton, Angela AU - Thornton A FAU - Jiang, Feng AU - Jiang F FAU - Broaddus, Russell R AU - Broaddus RR FAU - Sun, Charlotte C AU - Sun CC FAU - Lu, Karen H AU - Lu KH FAU - Sood, Anil K AU - Sood AK FAU - Gershenson, David M AU - Gershenson DM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060928 PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (Neoplasm Proteins) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (PTK6 protein, human) SB - IM MH - Cell Line, Tumor MH - Cloning, Molecular MH - Cystadenocarcinoma, Serous/*enzymology/pathology MH - Female MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Neoplasm Proteins/*biosynthesis/genetics/metabolism MH - Ovarian Neoplasms/*enzymology/genetics/pathology MH - Protein-Tyrosine Kinases/*biosynthesis/genetics/metabolism EDAT- 2006/07/21 09:00 MHDA- 2007/04/21 09:00 CRDT- 2006/07/21 09:00 PHST- 2006/07/21 09:00 [pubmed] PHST- 2007/04/21 09:00 [medline] PHST- 2006/07/21 09:00 [entrez] AID - 2953 [pii] AID - 10.4161/cbt.5.9.2953 [doi] PST - ppublish SO - Cancer Biol Ther. 2006 Sep;5(9):1136-41. doi: 10.4161/cbt.5.9.2953. Epub 2006 Sep 28.