Activation of Src Kinase in Primary Colorectal Carcinoma

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dc.contributor.author Abdalla, Eddie
dc.contributor.author Allgayer, Heike
dc.contributor.author Boyd, Douglas
dc.contributor.author Heiss, Markus
dc.contributor.author Curley, Steven
dc.contributor.author Gallick, Gary
dc.date.accessioned 2015-11-10T09:43:41Z
dc.date.available 2015-11-10T09:43:41Z
dc.date.copyright 2002
dc.date.issued 2015-11-10
dc.identifier.issn 0008-543X en_US
dc.identifier.uri http://hdl.handle.net/10725/2510
dc.description.abstract BACKGROUND. The specific activity of the non-receptor protein tyrosine kinase, Src, is increased in the majority of colon and rectal adenocarcinomas compared to normal mucosa. However, the prognostic significance of this difference is unknown. The objective of the current study was to determine if Src activity is a marker for poor clinical prognosis in colon carcinoma patients. As Src activation leads to expression of urokinase/plasminogen activator receptor (u-PAR), expression of Src and u-PAR were correlated with patient survival. METHODS. Tumors and adjacent normal colonic mucosae from 45 patients with colorectal carcinoma were screened for Src activity by the immune complex kinase assay. Expression of u-PAR was determined by enzyme linked immunoabsorbent assay. The primary tumor-to-normal mucosa ratios of activity were compared following classification and regression tree (CART) analysis to determine the prognostic significance of elevated specific Src activity. Expression of u-PAR was correlated with Src activity. RESULTS. By CART analysis, Src activity in tumors elevated more than twofold over normal mucosa was significant. Increased Src activity significantly correlated with Dukes stage, pT and pN classification, and increased u-PAR levels (P 0.001). Kaplan Meier analysis showed a significant association between elevated Src activity and shorter overall survival of all patients (P 0.0004) and of Dukes Stage A-C patients (P 0.0037). In patients who underwent curative resection, a significant correlation with a decreased disease-free survival rate was found (P 0.0001). Multivariate analysis revealed that elevated Src activity was a prognostic parameter independent of M classification (P 0.0125, relative risk 3.54, 95% confidence interval 1.31 – 9.76). CONCLUSIONS. Src activity is an independent indicator of poor clinical prognosis in all stages of human colon carcinoma. These data suggest that Src-specific inhibitors may have a therapeutic role in inhibiting tumor progression and metastasis, and that measurement of Src activity may aid in selection of early stage patients for adjuvant therapy. C en_US
dc.language.iso en en_US
dc.title Activation of Src Kinase in Primary Colorectal Carcinoma en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 201100945 en_US
dc.author.woa N/A en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Cancer en_US
dc.journal.volume 94 en_US
dc.journal.issue 2 en_US
dc.article.pages 344-351 en_US
dc.keywords Src en_US
dc.keywords Urokinase-type plasminogen activator receptor en_US
dc.keywords Colorectal carcinoma en_US
dc.keywords Protein tyrosine kinase en_US
dc.identifier.doi http://dx.doi.org/10.1002/cncr.10221 en_US
dc.identifier.ctation Allgayer, H., Boyd, D. D., Heiss, M. M., Abdalla, E. K., Curley, S. A., & Gallick, G. E. (2002). Activation of Src kinase in primary colorectal carcinoma. Cancer, 94(2), 344-351. en_US
dc.author.email eddie.abdalla@lau.edu.lb
dc.identifier.url http://onlinelibrary.wiley.com/doi/10.1002/cncr.10221/full

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