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BREAST CANCER PROGRESSION AND METASTASIS: DISCOVERY OF NOVEL GENES AND THEIR FUNCTIONAL STUDY

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abstract
Breast cancer is one of major public health problem worldwide. However, the underlying molecular mechanism of breast cancer progression and metastasis is not well understood. Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer which could progress to or recur as invasive breast cancer. To identify the novel regulators of DCIS progression, we performed gene expression analysis of syngeneic cell lines MCF10A, DCIS.com and MCF10CA and cross-referenced the targets using patient cohorts. By comparing gene expression between MCF10A and DCIS.com cell line, we identified ID2 as a regulator of DCIS initiation. ID2 promoted DCIS formation by enhancing cancer stemness of premalignant cells. On the other hand, we compared the DCIS.com and invasive breast cancer cell line, MCF10CA, and identified INHBA and GJB2 as novel regulators of aggressive phenotype. These 2 genes regulated migration, colonization and stemness of invasive cancer cells. Finally, we identified an ID2 inhibitor, natural compound Helichrysetin.
subject
Breast cancer
Cancer
Metastasis
Prognosis
contributor
Liu, Yin (author)
Watabe, Kounosuke (committee chair)
Lo, Hui-Wen (committee member)
Vidi, Pierre-Alexander (committee member)
Miller, Lance D (committee member)
Metheny-Barlow, Linda (committee member)
date
2018-05-24T08:36:03Z (accessioned)
2019-05-23T08:30:13Z (available)
2018 (issued)
degree
Cancer Biology (discipline)
embargo
2019-05-23 (terms)
identifier
http://hdl.handle.net/10339/90710 (uri)
language
en (iso)
publisher
Wake Forest University
title
BREAST CANCER PROGRESSION AND METASTASIS: DISCOVERY OF NOVEL GENES AND THEIR FUNCTIONAL STUDY
type
Dissertation

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