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Suppression of mammary tumorigenesis by a Gemini vitamin D analog and a synthetic truterpenoid

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TitleInfo
Title
Suppression of mammary tumorigenesis by a Gemini vitamin D analog and a synthetic truterpenoid
Name (type = personal)
NamePart (type = family)
So
NamePart (type = given)
Jae Young
NamePart (type = date)
1980-
DisplayForm
Jae Young So
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Suh
NamePart (type = given)
Nanjoo
DisplayForm
Nanjoo Suh
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Minden
NamePart (type = given)
Audrey
DisplayForm
Audrey Minden
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Liu
NamePart (type = given)
Fang
DisplayForm
Fang Liu
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Cai
NamePart (type = given)
Li
DisplayForm
Li Cai
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Studzinski
NamePart (type = given)
George P.
DisplayForm
George P. Studzinski
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)
2013
DateOther (qualifier = exact); (type = degree)
2013-01
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Breast cancer is a heterogeneous disease categorized into multiple subtypes, including luminal, HER2-positive and basal-like subtypes, which exhibit distinct gene signatures and clinical outcomes. Basal-like breast cancer has the worst prognosis among these subtypes and has no clinically approved targeted therapy. While HER2-targeting therapy with a humanized HER2 monoclonal antibody markedly improved the prognosis of HER2-positive breast cancer, the de novo and acquired resistance against the antibody has emerged as a new challenge for patients with HER2-positive breast cancer. MCF10 cell lines, a human breast cancer progression model representing the basal-like breast cancer subtype, were employed to identify key proteins involved in different stages of mammary tumorigenesis. Increased levels of IGF-IR, cyclin D1 and c-Myc were associated with HRAS-driven transformation. Higher levels of pErk, pAkt, STAT3 and Pak4 contribute to tumorigenicity in vivo, whereas CD44, HER2, COX-2 and Smad4 may be involved in the breast cancer progression. The MCF10DCIS.com cells, one of the MCF10 cell lines, highly express a breast cancer stem cell marker, CD44. A Gemini vitamin D analog BXL0124 markedly repressed the CD44 protein level and the growth of MCF10DCIS.com xenograft tumors. CD44 overexpression was correlated with invasive phenotype in MCF10DCIS.com cells, and the repression of CD44 by BXL0124 contributed to the inhibition of cell invasion. STAT3, which interacts directly with CD44, was identified as a key downstream signaling molecule affected by BXL0124 in MCF10DCIS.com cells. The CD44 knockdown study supported the critical role of CD44-STAT3 signaling in the invasive potential of MCF10DCIS.com cells in vitro and in vivo. The anti-cancer effects of BXL0124 and a synthetic triterpenoid CDDO-Im on HER2-positive breast cancer were tested in MMTV-HER2/neu transgenic mice. BXL0124, CDDO-Im and their combination delayed the development of mammary tumors and markedly inhibited the activation of HER2 and EGFR as well as their downstream molecules, such as Erk, Src and c-Myc in MMTV-HER2/neu mammary tumors. In conclusion, we demonstrated therapeutic potential of Gemini vitamin D analog BXL0124 targeting CD44-STAT3 signaling in basal-like breast cancer. In addition, we found anti-cancer activities of BXL0124 and CDDO-Im in HER2-positive breast cancer and potentially additive effects of their combination.
Subject (authority = RUETD)
Topic
Pharmacology, Cellular and Molecular
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4429
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xvii, 155 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Jae Young So
Subject (authority = ETD-LCSH)
Topic
Breast--Cancer--Treatment
Subject (authority = ETD-LCSH)
Topic
Vitamin D--Therapeutic use
Identifier (type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000067845
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/T3JW8CK7
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
So
GivenName
Jae Young
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2012-12-17 18:39:55
AssociatedEntity
Name
Jae Young So
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)
2013-01-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2013-08-02
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after August 2nd, 2013.
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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