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REDEFINING THE MOLECULAR BASIS OF EPITHELIAL MESENCHYMAL TRANSITION IN BREAST CANCER METASTASIS
Zhai, Yubo
Zhai, Yubo
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Thesis/Dissertation
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2013
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Biochemistry
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http://dx.doi.org/10.34944/dspace/3898
Abstract
Metastasis is a multi-step process that begins with cancer cells migrating and invading away from the primary tumor site and extravasating into distant organs to establish a secondary tumor. The loss of epithelial expression markers by neoplastic breast cancer cells in the primary tumor is believed to play a pivotal role during breast cancer metastasis. This phenomenon is the hallmark of the epithelial mesenchymal transition (EMT) process. Gene expression microarrays were performed to investigate key functional elements on an in vitro metastasis model derived from human breast epithelial cells (MCF-10F) treated with 17-beta estradiol. Functional profiling of dysregulated genes revealed progressive changes in the integrin signaling pathway, and epithelial-mesenchymal transition. In tumorigenic cells, the levels of E-cadherin, desmoplakin and various keratins were low, whereas SLUG, integrin beta 1 and fibronectin were high. SLUG, a zinc finger transcription factor acting as a transcriptional repressor, was defined as a promising target which led us establishing a SLUG-centered hypothetical pathway from the profile of dysregulated genes.
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