Regulation and Function of Caveolin-1 in Colorectal Carcinogenesis

Persistent Link:
http://hdl.handle.net/10150/194031
Title:
Regulation and Function of Caveolin-1 in Colorectal Carcinogenesis
Author:
Basu Roy, Upal Kunal
Issue Date:
2007
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Colon cancer is the second leading cause of cancer deaths in the United States of America. It is caused by the accumulation of mutations in tumor suppressors and oncogenes. The APC tumor suppressor is mutated in most diagnosed cases of colorectal cancer. Mutations in the K-RAS oncogene occur at later stages of colon cancer progression. In the present study, the transcriptional regulation of a novel target of these two genes, caveolin-1, was studied. Caveolin-1 is transcriptionally regulated by the APC tumor suppressor gene, via induction of its inducer, FOXO1 and the suppression of its transcriptional repressor, C-MYC. An activated K-RAS oncogene induces caveolin-1 transcription via activation of the P-I3 Kinase pathway. In addition to transcriptional regulation of caveolin-1, the influence of caveolin-1 expression on cellular phenotypes like signal transduction and polyamine uptake were assessed. The present studies demonstrate that caveolin-1 expression affects basal levels of AKT and ERK signaling, with an increased signaling associated with caveolin-1 expression in these colon tumor-derived cells. In addition, caveolin-1 expression positively affects signaling in response to an inflammatory stimulus like TPA. Interestingly, caveolin-1 expression leads to a decrease in the uptake of pro-tumorigenic molecules like polyamines, in the colon cell lines tested. Taken together, the data from this study suggests that caveolin-1 is transcriptionally regulated by the APC and the K-RAS gene at different stages of colorectal tumorigenesis and this in turn, leads to different phenotypes influenced by caveolin-1 expression.
Type:
text; Electronic Dissertation
Keywords:
Molecular & Cellular Biology
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Molecular & Cellular Biology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Gerner, Eugene W.

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleRegulation and Function of Caveolin-1 in Colorectal Carcinogenesisen_US
dc.creatorBasu Roy, Upal Kunalen_US
dc.contributor.authorBasu Roy, Upal Kunalen_US
dc.date.issued2007en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractColon cancer is the second leading cause of cancer deaths in the United States of America. It is caused by the accumulation of mutations in tumor suppressors and oncogenes. The APC tumor suppressor is mutated in most diagnosed cases of colorectal cancer. Mutations in the K-RAS oncogene occur at later stages of colon cancer progression. In the present study, the transcriptional regulation of a novel target of these two genes, caveolin-1, was studied. Caveolin-1 is transcriptionally regulated by the APC tumor suppressor gene, via induction of its inducer, FOXO1 and the suppression of its transcriptional repressor, C-MYC. An activated K-RAS oncogene induces caveolin-1 transcription via activation of the P-I3 Kinase pathway. In addition to transcriptional regulation of caveolin-1, the influence of caveolin-1 expression on cellular phenotypes like signal transduction and polyamine uptake were assessed. The present studies demonstrate that caveolin-1 expression affects basal levels of AKT and ERK signaling, with an increased signaling associated with caveolin-1 expression in these colon tumor-derived cells. In addition, caveolin-1 expression positively affects signaling in response to an inflammatory stimulus like TPA. Interestingly, caveolin-1 expression leads to a decrease in the uptake of pro-tumorigenic molecules like polyamines, in the colon cell lines tested. Taken together, the data from this study suggests that caveolin-1 is transcriptionally regulated by the APC and the K-RAS gene at different stages of colorectal tumorigenesis and this in turn, leads to different phenotypes influenced by caveolin-1 expression.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectMolecular & Cellular Biologyen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMolecular & Cellular Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairGerner, Eugene W.en_US
dc.contributor.committeememberPayne, Claire M.en_US
dc.contributor.committeememberSchroeder, Joyce A.en_US
dc.contributor.committeememberBowden, G. Timothyen_US
dc.contributor.committeememberMartinez, Jesse D.en_US
dc.identifier.proquest2254en_US
dc.identifier.oclc659747422en_US
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