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OVER-EXPRESSION OF EPHB4 BY CANCER CELLS PROVIDES SURVIVAL ADVANTAGE BY INTERRUPTING DEATH RECEPTOR-MEDIATED APOPTOTIC PATHWAYS
by
Ram Kumar Subramanyan
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PATHOBIOLOGY)
December 2006
Copyright 2006 Ram Kumar Subramanyan
Object Description
| Title | Over-expression of EphB4 by cancer cells provides survival advantage by interrupting death receptor-mediated apoptotic pathways |
| Author | Subramanyan, Ram Kumar |
| Author email | rsubrama@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2006-06-09 |
| Date submitted | 2006 |
| Restricted until | Unrestricted |
| Date published | 2006-10-09 |
| Advisor (committee chair) | Gill, Parkash S. |
| Advisor (committee member) | Epstein, Alan L. |
| Abstract | An increasing body of evidence suggests overexpression of Eph receptor tyrosine kinases in tumors. However, their function in tumor biology is unknown. This thesis proposal evaluates the expression and biological significance of EphB4 in eight different epithelial cancers. Consistently, membranous expression of EphB4 was observed at much higher levels in tumor tissue compared to adjacent normal tissue, with a trend towards increased expression in higher grade, stage and proliferative front of tumors. EphB4 expression was upregulated by oncogenes such as EGFR, HER-2/neu and Akt, and downregulated by tumor suppressors such as PTEN, p53 and APC. EphB4 provides direct survival signals to tumor cells both in vitro and in vivo by interrupting extrinsic apoptotic pathways. Expression of the extracellular domain of EphB4 is sufficient for tumor cells to overcome apoptotic signals from the TRAIL-death receptor pathway. These results confirm that targeted overexpression of EphB4 on epithelial tumor cells provides a survival advantage to tumors by interrupting death-receptor-mediated apoptosis. |
| Keyword | EphB4; apoptosis; angiogenesis; TRAIL; death receptor |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m89 |
| Rights | Subramanyan, Ram Kumar |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Subramanyan-20061009 |
| Archival file | uscthesesreloadpub_Volume26/etd-Subramanyan-20061009.pdf |
Description
| Title | Page 1 |
| Full text | OVER-EXPRESSION OF EPHB4 BY CANCER CELLS PROVIDES SURVIVAL ADVANTAGE BY INTERRUPTING DEATH RECEPTOR-MEDIATED APOPTOTIC PATHWAYS by Ram Kumar Subramanyan A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PATHOBIOLOGY) December 2006 Copyright 2006 Ram Kumar Subramanyan |
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