In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1271-1271
Abstract:
Aberrations in protein kinase activity and the consequent deregulation of downstream signaling pathways are considered a hallmark of oncogenesis. The purpose of this study was to investigate the phosphorylation state, the ultimate readout of dysregulated activity, of protein tyrosine kinases in ovarian tumors. An innovative Luminex multiplex platform was employed to systematically determine phosphorylation status of protein tyrosine kinases in a total of 69 protein lysates derived from normal human ovarian surface epithelial (HOSE) cells, ovarian tumors, and cancer cell lines. Significance Analysis of Microarrays (SAM) was performed to identify the signature of phosphorylated kinases with statistical significance. Profiling results were confirmed by using phosphor-specific kinase antibodies in immunoblot analysis of the profiled lysates and immunohistochemistry on formalin-fixed paraffin-embedded archived ovarian and fallopian tissues, as well as immunofluorescence of ovarian cancer cells growing as monolayer or 3D Matrigel cell cultures. A signature of twenty-two phosphorylated protein tyrosine kinases was identified by SAM analysis of the profiling data. Spleen Tyrosine Kinase (SYK), a novel tyrosine kinase included in the signature, was found significantly phosphorylated in lysates from ovarian cancer tissues compared to normal tissues by both Western blot analysis and immunohistochemistry on 94 clinical ovarian tissues (P=0.024). SYK phosphorylation was also identified in tubal intraepithelial carcinomas, the hypothesized precursors of high-grade serous ovarian carcinomas. However, SYK activation was not observed in ovarian cancer cell lines growing as attached monolayer cells, but was present when they grew as mouse xenografts or in 3D Matrigel in vitro cultures. We are the first to report that SYK, an extensively investigated tyrosine kinase in hematopoietic cells, is aberrantly phosphorylated and activated in ovarian cancer. SYK phosphorylation in ovarian cancer might be induced by extracellular stimuli that are exclusively present in the tumor microenvironment. These findings provide additional options in targeted therapy for ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1271. doi:1538-7445.AM2012-1271
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2012-1271
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2012
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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