AP-1 regulation during malignant progression of mouse keratinocyte cells

Persistent Link:
http://hdl.handle.net/10150/282562
Title:
AP-1 regulation during malignant progression of mouse keratinocyte cells
Author:
Joseloff, Elizabeth, 1969-
Issue Date:
1997
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:
The mouse skin model that has been used to study skin carcinogenesis can be divided into three stages: initiation, promotion, and progression. One genetic change observed during tumor promotion and malignant progression is increased transactivation of the transcription factor AP-1. AP-1 consists of Jun (c-Jun, Jun B, Jun D) and Fos (c-Fos, Fos B, Fra-1, Fra-2) proteins that form Jun:Jun homodimers or Jun:Fos heterodimers. AP-1 binds to a consensus cis-promoter element, the TRE, and transcriptionally regulate a number of genes with various biological functions. By studying the benign mouse keratinocyte cells, 308, and its malignant variant, 10Gy5, it has been shown that 10Gy5 cells have elevated AP-1 activity compared to 308 cells. Reduced AP-1 transactivation in 10Gy5 cells has been correlated with suppression of its malignant phenotype. This research examined the differential AP-1 transactivation in benign 308 and malignant 10Gy5 cells. By examing mechanisms of AP-1 regulation in the two cell lines, differences were observed with post-translational modifications of AP-1. There were differences in phosphorylation of one of the AP-1 family members, Jun B. In addition, AP-1 proteins in 10Gy5 cells appear to be in a fully reduced state, unlike AP-1 proteins in 308 cells. A third difference that was observed was in Jun B steady state protein levels, with decreased Jun B protein in malignant 10Gy5 compared to benign 308 cells. Reduced Jun B protein in 10Gy5 cells was the result of decreased Jun B protein synthesis. Jun B protein may inhibit AP-1 transactivation and cell proliferation. Experiments were performed to determine whether Jun B protein could modulate AP-1 transactivation, cell growth, and tumor formation in 308 and 10Gy5 cells. Altering Jun B protein levels in these keratinocytes affected AP-1 transactivation. Overexpression of Jun B protein in malignant 10Gy5 cells corresponded to an inhibition of cell growth and tumor development. However, overexpression of Jun B protein in 10Gy5 cells was not sufficient to reverse the malignancy, indicating that additional genetic changes are involved in malignant conversion of these keratinocytes. The results of this research suggest that Jun B protein levels may be important during malignant progression of mouse skin.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Biology, Molecular.; Biology, Cell.; Health Sciences, Oncology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Interdisciplinary Program inCancer Biology
Degree Grantor:
University of Arizona
Advisor:
Bowden, G. T.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleAP-1 regulation during malignant progression of mouse keratinocyte cellsen_US
dc.creatorJoseloff, Elizabeth, 1969-en_US
dc.contributor.authorJoseloff, Elizabeth, 1969-en_US
dc.date.issued1997en_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.abstractThe mouse skin model that has been used to study skin carcinogenesis can be divided into three stages: initiation, promotion, and progression. One genetic change observed during tumor promotion and malignant progression is increased transactivation of the transcription factor AP-1. AP-1 consists of Jun (c-Jun, Jun B, Jun D) and Fos (c-Fos, Fos B, Fra-1, Fra-2) proteins that form Jun:Jun homodimers or Jun:Fos heterodimers. AP-1 binds to a consensus cis-promoter element, the TRE, and transcriptionally regulate a number of genes with various biological functions. By studying the benign mouse keratinocyte cells, 308, and its malignant variant, 10Gy5, it has been shown that 10Gy5 cells have elevated AP-1 activity compared to 308 cells. Reduced AP-1 transactivation in 10Gy5 cells has been correlated with suppression of its malignant phenotype. This research examined the differential AP-1 transactivation in benign 308 and malignant 10Gy5 cells. By examing mechanisms of AP-1 regulation in the two cell lines, differences were observed with post-translational modifications of AP-1. There were differences in phosphorylation of one of the AP-1 family members, Jun B. In addition, AP-1 proteins in 10Gy5 cells appear to be in a fully reduced state, unlike AP-1 proteins in 308 cells. A third difference that was observed was in Jun B steady state protein levels, with decreased Jun B protein in malignant 10Gy5 compared to benign 308 cells. Reduced Jun B protein in 10Gy5 cells was the result of decreased Jun B protein synthesis. Jun B protein may inhibit AP-1 transactivation and cell proliferation. Experiments were performed to determine whether Jun B protein could modulate AP-1 transactivation, cell growth, and tumor formation in 308 and 10Gy5 cells. Altering Jun B protein levels in these keratinocytes affected AP-1 transactivation. Overexpression of Jun B protein in malignant 10Gy5 cells corresponded to an inhibition of cell growth and tumor development. However, overexpression of Jun B protein in 10Gy5 cells was not sufficient to reverse the malignancy, indicating that additional genetic changes are involved in malignant conversion of these keratinocytes. The results of this research suggest that Jun B protein levels may be important during malignant progression of mouse skin.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectBiology, Molecular.en_US
dc.subjectBiology, Cell.en_US
dc.subjectHealth Sciences, Oncology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineInterdisciplinary Program inCancer Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBowden, G. T.en_US
dc.identifier.proquest9817336en_US
dc.identifier.bibrecord.b38268504en_US
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