MUC1 as a Biomarker for TGF-ß1 Inhibition: Investigating the Role of MUC1 in the Switch of TGF-ß1 Function from a Tumor Suppressor to a Tumor Promoter in Pancreatic Ductal Adenocarcinoma

Overview

With a 5-year survival rate of only 6%, pancreatic ductal adenocarcinoma (PDA) is the 4th leading cause of cancer related deaths in the United States. Transforming Growth Factor-ß1 (TGF-ß1), a growth factor commonly over-expressed in PDA, can act both as a tumor suppressor and a promoter of tumor progression. At early stages of tumorigenesis, TGF-ß1 acts as tumor suppressor via inducing apoptosis of cancer cells. However, as the tumor progresses, biochemical changes within the tumor microenvironment allow TGF-ß1 to stimulate tumor progression by initiating epithelial-to-mesenchymal transition (EMT). This allows cancer cells to invade into neighboring healthy tissues and also metastasize to distant organs. In parallel, mucin 1 (MUC1), a circulatory, transmembrane glycoprotein, is frequently over-expressed in more than 90% of PDA patients. I hypothesize that signaling through MUC1 supports TGF-ß1 induced EMT and invasion and inhibits TGF-ß1 induced apoptosis. Western blotting technique was used to determine the endogenous expression of MUC1 and TGF-ß1 receptor I and II with a panel of cell lines. Migration Assay and Flow Cytometry Cell Cycle Analysis with Propidium Iodide staining were used to test the effects of MUC1 on TGF-ß1 induced apoptosis and EMT with a panel of cell lines. These results showed that signaling through MUC1 leads to down regulation of TGF-ß1-induced apoptosis and up regulation in TGF-ß1-induced invasion. These results support my hypothesis that MUC1 regulates TGF-ß1 signaling pathways, switching TGF-ß1 from a tumor suppressor to a tumor promoter. Thus, MUC1 up regulation in PDA could help deduce the efficacy of therapeutic reagents that target TGF-ß1 and its downstream partners by determining TGF-ß1 as either tumor suppressive or promoting.

Awards (1)

• Second Award of $2,000 $2,000

Competition history

• ISEF 2014 Mathematics · Entry ME011

Resources

• ISEF abstract page ↗

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