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The Function Of Ephrina1 In Glioma

Posted on:2008-06-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:D P LiuFull Text:PDF
GTID:1104360215955094Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
THE FUNCTION OF EPHRINA1 IN GLIOMAEph receptors, the largest receptor tyrosine kinases, and their ephrin ligands play important roles in axon guidance and cell migration during development of the nervous system. Recently, these molecules are also found involved in tumorigenesis of different kinds of cancers. In this study, we demonstrated that expression of ephrin-A1 was dramatically down-regulated in glioma cell lines as well as in primary gliomas comparing to the matched normal tissues. Forced expression of ephrin-A1 attenuated cell migration, cell proliferation, and adhesion-independent growth in human glioma U251 cells. Overexpression of ephrin-A1 stimulated activation of EphA2, a receptor for ephrin-A1 and an oncoprotein, by phosphorylation and leaded the latter to degradation. Furthermore, focal adhesion kinase (FAK), a known downstream molecule of EphA2, was also down-regulated in those ephrin-A1 transfected cells. These results suggested that ephrin-A1 served as a critical negative regulator in the tumorigenesis of gliomas by down-regulating EphA2 and FAK, which may provide potential valuable targets for therapeutic intervention.PROTEOMIC ANALYSIS OF ESOPHAGEAL SQUAMOUS CELL CARCINOMAEsophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancers in China, and characterized with high morbidity and mortality. So far, the diagnosis of ESCC is mainly dependent on the alterations in esophageal histology, but most cases of ESCC with low stage do not display visible histological abnormalities. Therefore deep understanding the mechanism of ESCC progression and seeking stage-specific molecules might improve the diagnosis and therapy for ESCC. In this study, we used proteomics to analyze ESCC tissues with classification by TNM stage, and determined the proteomic features correlated with ESCC progression (from stage I to III). Proteins that exhibited significantly differential expressions between ESCC and corresponding normal esophageal tissues were identified by using mass spectrometry. The identified proteins with differentiated expression mainly fell into three protein categories (i.e. cytoskeleton system associated proteins, metabolism enzymes, and heat shock proteins). In addition, real-time PCR displayed that some molecules were associated with tumor stages in mRNA level, such as enolase 1, chromosome 1 open reading frame 10, elastase inhibitor, alpha B crystalline, stress induced phosphoprotein 1, and squamous cell carcinoma antigen 1. Altogether, these data provided further information on ESCC progression and potential drug targets for ESCC clinical therapy.
Keywords/Search Tags:ephrin-A1, EphA2, FAK, gliomas, esophageal squamous cell carcinoma, TNM stage, two-dimensional gel electrophoresis
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