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The Role of Osteopontin in Claudin-low Mammary Tumorigenesis

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Title: The Role of Osteopontin in Claudin-low Mammary Tumorigenesis
Author: Saleh, Soadad
Department: Department of Biomedical Sciences
Program: Biomedical Sciences
Advisor: Moorehead, Roger
Abstract: Osteopontin (OPN) is a cell-secreted phospho-glycoprotein that is implicated in both physiological and pathological processes in the body. Tumors of several cancer types, including breast cancer, exhibit high levels of OPN expression. Elevated expression of OPN in breast cancer is associated with increased tumor invasiveness and poor prognosis. Claudin-low breast cancer is the last molecular subtype of triple negative breast cancers to be identified; it has a prevalence of 7-14% and is associated with poor prognosis. Our laboratory screened for OPN expression in a murine model of claudin-low mammary tumors and found a 15-fold increase of OPN expression in claudin-low mammary tumors compared to normal mammary tissues. In this study, OPN downregulation via RNA interference (RNAi) reduced claudin-low tumor cell proliferation and survival. Additionally, short-term OPN knockdown impaired cellular migration and invasion in vitro. Furthermore, this study is the first to demonstrate OPN inhibition increases AKT and ERK1/2 kinase activity in claudin-low tumor cells. These data suggest that OPN may be a promising therapeutic target for triple negative breast cancers.
Date: 2015-01
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