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Role of endogenous IGFBP-3 in mammary epithelial cell apoptosis
Descriptive
TitleInfo
Title
Role of endogenous IGFBP-3 in mammary epithelial cell apoptosis
Name
(type = personal)
NamePart
(type = family)
Agostini-Dreyer
NamePart
(type = given)
Allyson M.
NamePart
(type = date)
1986-
DisplayForm
Allyson Agostini-Dreyer
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Cohick
NamePart
(type = given)
Wendie S
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Wendie S Cohick
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Brasaemle
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(type = given)
Dawn
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Dawn Brasaemle
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Bello
NamePart
(type = given)
Nicholas T
DisplayForm
Nicholas T Bello
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Thomas
NamePart
(type = given)
TJ
DisplayForm
TJ Thomas
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Bagnell
NamePart
(type = given)
Carol
DisplayForm
Carol Bagnell
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
outside member
Name
(type = corporate)
NamePart
Rutgers University
Role
RoleTerm
(authority = RULIB)
degree grantor
Name
(type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm
(authority = RULIB)
school
TypeOfResource
Text
Genre
(authority = marcgt)
theses
OriginInfo
DateCreated
(qualifier = exact)
2014
DateOther
(qualifier = exact);
(type = degree)
2014-05
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
The overall goal of this work was to investigate a role for endogenous insulin-like growth factor binding protein-3 (IGFBP-3) in intrinsic apoptosis in non-transformed bovine mammary epithelial cells (MEC). IGFBP-3 was produced and secreted in response to anisomycin (ANS), an activator of the intrinsic apoptotic pathway. Knock-down of IGFBP-3 with small interfering (si)RNA attenuated ANS-induced apoptosis, establishing a role for IGFBP-3 in MEC apoptosis. A nuclear function for IGFBP-3 was suggested by findings from cell fractionation experiments showing that ANS induced nuclear accumulation of IGFBP-3. In MECs, knock-down of IGFBP-3 attenuated ANS-induced phosphorylation and nuclear export of the orphan nuclear receptor Nur77. Co-immunoprecipitation experiments revealed an association between IGFBP-3 and Nur77 in ANS-treated cells, but not in untreated controls, suggesting that IGFBP-3 exerts its nuclear effects through physical association with Nur77. A second goal of the thesis was to determine the mechanism by which IGFBP-3 localizes to the nucleus in bovine MEC. An inhibitor of endocytosis had no effect on nuclear localization of IGFBP-3 while an inhibitor of secretion enhanced nuclear IGFBP-3. Together these data indicate that nuclear IGFBP-3 does not arise from secreted IGFBP-3 that is re-internalized. Since the molecular weight of glycosylated IGFBP-3 is near the cut-off for passive diffusion through nuclear pores, IGFBP-3 was tagged with GFP in order to determine if transport was a regulated process. ANS treatment of cells transfected with IGFBP-3-GFP increased the protein in the nucleus, indicating that nuclear import of IGFBP-3 is a regulated event. An antibody specific to bovine IGFBP-3 was generated to enable co-immunoprecipitation experiments. An association between IGFBP-3 and nuclear transport protein importin-β was found only in ANS-treated cells. Inhibition of importin-β attenuated nuclear import of IGFBP-3-GFP, establishing a role for importin-β in nuclear transport of IGFBP-3. In summary, these data indicate that nuclear localization of IGFBP-3 plays a role in intrinsic apoptosis in MEC and are the first to establish a mechanism for nuclear transport of endogenous IGFBP-3.
Subject
(authority = RUETD)
Topic
Nutritional Sciences
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_5406
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xi, 144 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Allyson M. Agostini-Dreyer
Subject
(authority = ETD-LCSH)
Topic
Somatomedin
Subject
(authority = ETD-LCSH)
Topic
Epithelial cells
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
PhysicalLocation
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3BK19NP
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Agostini-Dreyer
GivenName
Allyson
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2014-04-08 10:53:00
AssociatedEntity
Name
Allyson Agostini-Dreyer
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
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.
RightsEvent
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2014-05-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2014-11-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2014.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
RULTechMD
(ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem
(VERSION = 5.1)
windows xp
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