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Effect of fetal alcohol exposure on mammary gland development and tumorigenesis in offspring

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TitleInfo
Title
Effect of fetal alcohol exposure on mammary gland development and tumorigenesis in offspring
Name (type = personal)
NamePart (type = family)
Crismale-Gann
NamePart (type = given)
Catina
NamePart (type = date)
1982-
DisplayForm
Catina Crismale-Gann
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Cohick
NamePart (type = given)
Wendie S.
DisplayForm
Wendie S. Cohick
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Suh
NamePart (type = given)
Nanjoo
DisplayForm
Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Zarbl
NamePart (type = given)
Helmut
DisplayForm
Helmut Zarbl
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Wood
NamePart (type = given)
Teresa L.
DisplayForm
Teresa L. Wood
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)
Alcohol exposure in utero increases susceptibility to carcinogen-induced mammary tumorigenesis in adult rats. However, the mechanisms underlying the enhanced susceptibility are not well understood. Pregnant Sprague Dawley rats were fed either a liquid diet containing 6.7% ethanol, an isocaloric liquid control diet, or rat chow ad libitum from gestation day 7 until parturition. At birth, female pups were cross-fostered to control dams. To determine if fetal alcohol alters the insulin-like growth factor (IGF)/estradiol (E2) axis in mammary gland development, we analyzed time points in pre-pubertal, pubertal, and mature F1 offspring. Mammary glands from alcohol-exposed animals displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Animals exposed to alcohol in utero exhibited increased hepatic IGF-I expression at all time points, increased mammary IGF-I expression at PND 20, and decreased mammary IGFBP-5 expression at PND 40. To investigate tumorigenesis, N-nitroso-N-methylurea (NMU) was administered on PND 50 to induce tumors and offspring were euthanized at 16 weeks post-NMU injection. The alcohol group developed more tumors overall as well as more hyperplasias and adenocarcinomas as compared to control groups. Alcohol-exposed animals developed more progesterone receptor positive tumors and exhibited increased Snail, IGF-II, and IGFBP-5, as well as decreased ERα tumor mRNA expression. To determine if fetal alcohol induces alterations in DNA methylation in the mammary gland, we assessed an IGFBP-5 promoter CpG island, the first CpG island in IGFBP-5 exon I, and an estrogen receptor (ER) α promoter/exon I CpG island in tumors and contralateral mammary glands as well as PND 40 mammary glands. While the IGFBP-5 promoter CpG island did not exhibit methylation, low levels of methylation were observed in the IGFBP-5 exon I CpG island in all tissues examined. Tumors from alcohol-exposed animals exhibited partial ERα methylation. These data indicate that alcohol exposure in utero may promote mammary tumorigenesis by inducing changes in the IGF and E2 systems during early development. Furthermore, alterations in PR, Snail, IGF-II, and IGFBP-5 may be involved in the underlying mechanisms of enhanced carcinogen-induced tumorigenesis observed in alcohol-exposed offspring.
Subject (authority = RUETD)
Topic
Cell and Developmental Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5459
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xv, 166 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Catina Crismale-Gann
Subject (authority = ETD-LCSH)
Topic
Fetal alcohol syndrome
Subject (authority = ETD-LCSH)
Topic
Carcinogenesis--Animal models
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3XP736Z
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
Crismale-Gann
GivenName
Catina
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-04-11 18:11:13
AssociatedEntity
Name
Catina Crismale-Gann
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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RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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