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Title: Cell interactions with fibronectin induce epithelial-mesenchymal transition of human mammary epithelial cells
Authors: Park, Jeongsook
Advisors: Schwarzbauer, Jean E
Contributors: Molecular Biology Department
Subjects: Molecular biology
Issue Date: 2012
Publisher: Princeton, NJ : Princeton University
Abstract: In the mammary gland, the stromal extracellular matrix (ECM) undergoes dramatic changes during development and in tumorigenesis. In particular, normal adult breast tissue is largely devoid of the ECM protein fibronectin (FN) whereas high FN levels have been detected in the stroma of breast tumors. Whether this high level of FN in the breast tumor tissue is the cause for the breast tumor or the result of the tumor progression is not investigated. Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose epithelial phenotypes and gain mesenchymal phenotype, and unregulated EMT is implied in cancer development. FN is a known EMT marker, but whether FN is contributes to EMT induction is not clear. We found that exposure of cultured mammary epithelial cells to exogenous FN induces an EMT response including induction of EMT markers such as FN, Snail, N-cadherin, vimentin, and the matrix metalloprotease MMP2 as well as acquisition of cell migratory behavior. We show that this FN-induced EMT response does not depend on the immediate early gene EGR-1 but depends on ERK signaling such that inhibition of ERK signaling upregulates FN and N-cadherin expression. We also show that activities of type I TGF beta receptor, Src, and p38MAPK are involved in the FN induction of EMT and that FN works via cooperation with downstream components of the TGF beta pathway. These results suggest that FN interactions with mammary epithelial cells promote an EMT response and therefore increased FN in breast cancer might be both a cause and a result of tumor initiation and/or progression.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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