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The role of hypoxia inducible factor...
~
Liao, Debbie.
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The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis.
Record Type:
Language materials, printed : Monograph/item
Title/Author:
The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis./
Author:
Liao, Debbie.
Description:
98 p.
Notes:
Adviser: Randall S. Johnson.
Contained By:
Dissertation Abstracts International68-04B.
Subject:
Biology, Cell. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3263071
ISBN:
9780549011712
The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis.
Liao, Debbie.
The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis.
- 98 p.
Adviser: Randall S. Johnson.
Thesis (Ph.D.)--University of California, San Diego, 2007.
Maintenance of oxygen homeostasis is crucial at both the cellular and systemic level in mammals. In poorly oxygenated (hypoxic) microenvironments adaptation to hypoxia involves changes in gene expression crucial for cell and tissue viability, known as the hypoxic response. The master regulator of the hypoxic response is the transcription factor Hypoxia Inducible Factor (HIF)-1alpha. Deregulation of HIF-1alpha activity has been shown to contribute to various pathologies including cancer. The aim of this dissertation is to elucidate the role of the hypoxic response, and the contribution of HIF-1alpha, during mammary gland tumor progression and metastasis.
ISBN: 9780549011712Subjects--Topical Terms:
1017686
Biology, Cell.
The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis.
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The role of hypoxia inducible factor-1alpha in mammary gland tumorigenesis.
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98 p.
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Adviser: Randall S. Johnson.
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Source: Dissertation Abstracts International, Volume: 68-04, Section: B, page: 2051.
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Thesis (Ph.D.)--University of California, San Diego, 2007.
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Maintenance of oxygen homeostasis is crucial at both the cellular and systemic level in mammals. In poorly oxygenated (hypoxic) microenvironments adaptation to hypoxia involves changes in gene expression crucial for cell and tissue viability, known as the hypoxic response. The master regulator of the hypoxic response is the transcription factor Hypoxia Inducible Factor (HIF)-1alpha. Deregulation of HIF-1alpha activity has been shown to contribute to various pathologies including cancer. The aim of this dissertation is to elucidate the role of the hypoxic response, and the contribution of HIF-1alpha, during mammary gland tumor progression and metastasis.
520
$a
The first chapter provides a brief overview of the hypoxic response and regulation of hypoxic gene expression by HIF-1alpha. A brief overview of normal mouse mammary gland development is discussed. Lastly, an introduction to the Polyoma Middle T (PyMT) transgenic mouse model of breast cancer used in these studies is provided.
520
$a
The second chapter describes the results of conditional deletion of HIF-1alpha in the tumor mammary epithelial cells (MECs) in the PyMT mouse model. Loss of HIF-1alpha resulted in delayed tumor onset due to reduced tumor cell proliferation. Loss of HIF-1alpha also resulted in significantly increased survival and reduced pulmonary metastasis. These findings demonstrated that the transcriptional activity of HIF-1alpha is a significant regulator of tumor progression and metastatic potential.
520
$a
The third chapter presents the regulation of E-cadherin expression by HIF-1alpha. Through Cre-mediated excision of the HIF-1alpha and VHL gene in tumor MECs, we demonstrate that E-cadherin is not transcriptionally regulated by HIF-1alpha. Instead, we show that HIF-1alpha activity promotes the internalization of E-cadherin protein through a VEGF/VEGFR1 autocrine signaling pathway during hypoxia stress.
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The concluding chapter describes the initial results and future direction of continuing work to elucidate the contribution of HIF-1alpha mediated cell-autonomous changes versus changes in the tumor microenvironment during mammary gland tumor progression and metastasis.
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School code: 0033.
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University of California, San Diego.
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committee member
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Firtel, Richard
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committee member
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Johnson, Randall S.,
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advisor
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Kamps, Mark
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committee member
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Mercola, Mark
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2007
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3263071
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