Viral jun oncogene serves as a suppressor of phorbol ester TPA induced tumor cell invasion and stromelysin gene expression

Persistent Link:
http://hdl.handle.net/10150/186681
Title:
Viral jun oncogene serves as a suppressor of phorbol ester TPA induced tumor cell invasion and stromelysin gene expression
Author:
Tsang, Tom Chun-Chang
Issue Date:
1994
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:
Carcinogenesis in the mouse skin is a multistep process involving initiation, promotion, and progression. In order for the benign papilloma cells that have been initiated and promoted to become malignant, genetic alterations are believed to be involved. The viral jun (v-jun) oncogene encodes a transcription factor that can participate in the transactivation of genes through the AP-1 complex. Evidence indicates that the ability of v-jun to transform cells and stimulate transcription depends on the cell type. The question that I have attempted to answer in my dissertation studies is whether expression of the v-jun gene in benign tumor forming mouse keratinocytes that already express an activated c-rasᴴᵃ oncogene would cause malignant progression. Our results showed that the v-jun transfection did not result in malignant progression; instead, we made the unexpected observation that the ability of these cells to invade reconstituted basement membrane matrix (in vitro) in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was suppressed. This phenomenon could partially be explained by the suppression of the induction by phorbol ester of expression of the metalloproteinase, stromelysin (transin). Of interest was the finding that TPA induction of other cellular genes known to be regulated by AP-1 was not inhibited in the benign tumor cells expressing v-jun. The suppressor activity shown by v-jun is different than that of other tumor suppressor genes in that it appears to be specific for the process of tumor invasion. A potential implication of this unexpected finding is that it may provide insight on how to develop cancer therapeutic strategies that can specifically inhibit tumor invasion. I have constructed a set of cassette cloning vectors that can be used for rapid adaptation of DNA restriction fragments. In addition, I have formulated a new model with regards to the mechanism of function for the 70 kDa family of heat shock proteins (hsp 70). This model proposes that hsp 70 serves as a cross-linker molecule between many cellular proteins and the cytoskeletal matrix, and this model may have significant implications on many cellular processes.
Type:
text; Dissertation-Reproduction (electronic)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Microbiology and Immunology; Graduate College
Degree Grantor:
University of Arizona
Committee Chair:
Bowden, G. Tim

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleViral jun oncogene serves as a suppressor of phorbol ester TPA induced tumor cell invasion and stromelysin gene expressionen_US
dc.creatorTsang, Tom Chun-Changen_US
dc.contributor.authorTsang, Tom Chun-Changen_US
dc.date.issued1994en_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.abstractCarcinogenesis in the mouse skin is a multistep process involving initiation, promotion, and progression. In order for the benign papilloma cells that have been initiated and promoted to become malignant, genetic alterations are believed to be involved. The viral jun (v-jun) oncogene encodes a transcription factor that can participate in the transactivation of genes through the AP-1 complex. Evidence indicates that the ability of v-jun to transform cells and stimulate transcription depends on the cell type. The question that I have attempted to answer in my dissertation studies is whether expression of the v-jun gene in benign tumor forming mouse keratinocytes that already express an activated c-rasᴴᵃ oncogene would cause malignant progression. Our results showed that the v-jun transfection did not result in malignant progression; instead, we made the unexpected observation that the ability of these cells to invade reconstituted basement membrane matrix (in vitro) in response to the phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was suppressed. This phenomenon could partially be explained by the suppression of the induction by phorbol ester of expression of the metalloproteinase, stromelysin (transin). Of interest was the finding that TPA induction of other cellular genes known to be regulated by AP-1 was not inhibited in the benign tumor cells expressing v-jun. The suppressor activity shown by v-jun is different than that of other tumor suppressor genes in that it appears to be specific for the process of tumor invasion. A potential implication of this unexpected finding is that it may provide insight on how to develop cancer therapeutic strategies that can specifically inhibit tumor invasion. I have constructed a set of cassette cloning vectors that can be used for rapid adaptation of DNA restriction fragments. In addition, I have formulated a new model with regards to the mechanism of function for the 70 kDa family of heat shock proteins (hsp 70). This model proposes that hsp 70 serves as a cross-linker molecule between many cellular proteins and the cytoskeletal matrix, and this model may have significant implications on many cellular processes.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.chairBowden, G. Timen_US
dc.contributor.committeememberKilkson, Reinen_US
dc.contributor.committeememberLam, Kit S.en_US
dc.contributor.committeememberGerner, Eugene W.en_US
dc.contributor.committeememberPowell, Marianne Broomeen_US
dc.identifier.proquest9426313en_US
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