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The role of Pak4 in tumorigenesis in vivo
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
The role of Pak4 in tumorigenesis in vivo
Identifier
ETD_2736
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056516
Language
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eng
Genre
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theses
Subject
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(authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Carcinogenesis
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Cells--Morphology
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Nude mouse--Research
Abstract
(type = abstract)
The Pak4 (P21 activated kinase) serine/threonine kinase is an important effector of Rho GTPases and has been implicated in the regulation of cell morphology and motility, as well as cell growth control. Our preliminary data showed that both Pak4 mRNA and protein are highly expressed in primary tumors and almost every tumor cell line, while there is a very low expression level in normal tissues. The goal of this thesis was to study the role of Pak4 in tumorigenesis. First, I investigated whether overexpression of Pak4 is sufficient to induce tumor formation. Fibroblast cell line NIH3T3 and immortalized mouse mammary epithelial cells (iMMECs) transfected with Pak4 were used. We found that overexpression of Pak4 in both cell lines led to formation of tumors in athymic mice. Furthermore, overexpression of Pak4 in iMMECs led to changes in 3D acinar architecture, including decreased central acinar cell death, abrogation of lumen formation, and cell polarity alteration. The results suggest that Pak4 can promote cell survival and proliferation, as well as alter cell shape and polarity, as part of the oncogenic process. Next, I investigated whether Pak4 is necessary for tumorigenesis in response to oncogenes such as Ras and Cdc42. Pak4 conventional knockout 3T3 cell lines and Pak4 conditional knockout 3T3 cell lines transfected with Ras or Cdc42 were used. We found that in cells transfected with oncogenic Ras, tumors grew more slowly and to a smaller size when Pak4 was deleted. In cells transfected with Cdc42, tumor formation was almost completely abrogated when Pak4 was absent. These results would be consistent with the role for Pak4 as a Cdc42 effector protein involved in signaling pathways leading from Cdc42 and its activators to transformation, and its critical role in cell survival and inhibition of apoptosis. This work shows for the first time that overexpression of Pak4 in epithelial cells leads to tumorigenesis in vivo, and that Pak4 is necessary for tumorigenesis in response to certain oncogenes. These findings make Pak4 an attractive target for cancer prevention or therapy.
PhysicalDescription
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electronic resource
Extent
ix, 148 p. : ill.
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Note
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Ph.D.
Note
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Includes bibliographical references
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Includes vita
Note
(type = statement of responsibility)
by Yingying Liu
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Liu
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Yingying
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author
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Yingying Liu
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Audrey
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chair
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Audrey Minden
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yang
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chung s
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chung s yang
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Conney
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Allan H
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Allan H Conney
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Zhou
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Renping
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Renping Zhou
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Chen
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Suzie
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Suzie Chen
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Rutgers University
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degree grantor
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Graduate School - New Brunswick
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school
OriginInfo
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2010
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2010-10
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xx
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Title
Rutgers University Electronic Theses and Dissertations
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ETD
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Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
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NjNbRU
Identifier
(type = doi)
doi:10.7282/T33T9H0X
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
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Name
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Liu
GivenName
Yingying
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DateTime
2010-05-18 15:40:53
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Name
Yingying Liu
Affiliation
Rutgers University. Graduate School - New Brunswick
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Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
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