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Fetal alcohol exposure increases susceptibility to tumorigenesis in the pituitary
Descriptive
TitleInfo
Title
Fetal alcohol exposure increases susceptibility to tumorigenesis in the pituitary
Name
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(type = family)
Jabbar
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(type = given)
Shaima
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1978-
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Shaima Jabbar
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author
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(type = family)
Sarkar
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Dipak
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Dipak Sarkar
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Advisory Committee
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chair
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Belden
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William
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William Belden
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Advisory Committee
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internal member
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(type = personal)
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(type = family)
Cohick
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(type = given)
Wendie
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Wendie Cohick
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Advisory Committee
Role
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(authority = RULIB)
internal member
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(type = personal)
NamePart
(type = family)
Reuhl
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(type = given)
Kenneth
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Kenneth Reuhl
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Advisory Committee
Role
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(authority = RULIB)
outside member
Name
(type = personal)
NamePart
(type = family)
Verzi
NamePart
(type = given)
Michael
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Michael Verzi
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Advisory Committee
Role
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(authority = RULIB)
outside member
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(type = corporate)
NamePart
Rutgers University
Role
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(authority = RULIB)
degree grantor
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School of Graduate Studies
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school
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Text
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theses
OriginInfo
DateCreated
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2017
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2017-10
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2017
Place
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xx
Language
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eng
Abstract
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Alcohol exposure during gestation increases susceptibility to the development of pituitary tumors in response to estrogen in rat offspring. While the mechanism underlie this effect is not fully understood, serum estradiol (E2) and pituitary aromatase mRNA expression are increased in fetal alcohol exposed (FAE) offspring, which suggests a role for the estrogen axis. To test our hypothesis, pregnant Fischer 344 rats were fed between gestational days 7 and 21 with a liquid diet containing alcohol (AF), pair-fed with isocaloric liquid diet (PF), or fed rat chow (AD). At 60 days of age, animals were ovariectomized and received a subcutaneous estradiol implant. Rats were sacrificed at various times point after estradiol implantation. At the time of sacrifice, pituitaries of these animals were inspected for tumor growth. Estradiol treatment time-dependently increased pituitary weight in AF group as compared to AD and PF groups. After 120 days of estradiol treatment, inspection of the pituitary revealed that most tumors in the AF group were hemorrhagic and showed expansion to the surrounding tissue. Pituitary tumors from FAE offspring showed strong nuclear p53 and Ki67 expression. Significantly higher mRNA levels of hemorrhage-associated genes and proteins (PTTG, FGF4 and MMP-9) and multipotency genes and proteins (SOX2, Oct4 and CD133) were also observed in pituitary tumor tissues from AF group as compared with PF and AD groups. To test whether FAE enhances the population of cancer stem cells (CSCs) in the pituitary in response to estradiol, pituitaries were collected, and plated in ultra-low plates to promote pituisphere formation. The growing spheres were enzymatically dissociated to permit serial passaging. Assessment of a panel of genes related to multipotency (OCT4, NANOG, KLF4, SOX2, CD133, CD44, nestin and CD34) indicated that mRNA and protein expression of most of these genes was significantly higher in pituitary cells derived from spheres of AF animals as compared to AD. Pituitary cells derived from spheres of AF animals showed higher cell proliferation, migration and colony formation rates as compared to the control group. The pituitary cells derived from AF spheres were able to grow in immunodeficient mice. These data suggest that alcohol feeding enhances pituitary tumor development, and may program the pituitary to express pluripotent and growth promoting molecules under the estrogenic influence to induce aggressive pituitary tumor.
Subject
(authority = RUETD)
Topic
Animal Sciences
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
Identifier
ETD_8441
PhysicalDescription
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(authority = gmd)
electronic resource
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application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiv, 102 p. : ill.)
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Subject
(authority = ETD-LCSH)
Topic
Fetal alcohol spectrum disorders
Subject
(authority = ETD-LCSH)
Topic
Pituitary gland
Note
(type = statement of responsibility)
by Shaima Jabbar
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(type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
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rucore10001600001
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3C53PZ6
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
RightsHolder
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Name
FamilyName
Jabbar
GivenName
Shaima
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
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(point = start)
2017-09-28 16:54:29
AssociatedEntity
Name
Shaima Jabbar
Role
Copyright holder
Affiliation
Rutgers University. School of Graduate Studies
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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