アクティブボード・２０１０年１月
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研究発表を行った学会；
・第３２回日本分子生物学会年会
　２００９年１２月９日〜１２日（横浜）

タイトル；SERINE PROTEASE INHIBITOR, KAZAL TYPE 1, INDUCES EGFR ACTIVATION AND CELL PROLIFERATION THROUGH EGFR/MAPK CASCADE.
　
発表者；　平松　さやか　氏
　　　（熊本大学　生命資源研究・支援センター　表現型クリニック分野）

Abstract；
Background & aims: Trypsin specific inhibitor, serine protease inhibitor, Kazal type 1 (SPINK1), is expressed in normal human pancreas and in a variety of tumors. SPINK1 increases the proliferation of a variety of cell lines and stimulates cell migration. However, its receptor and signaling pathways are not known yet. On the other hand, the epidermal growth factor receptor (EGFR) is overexpressed in pancreatic cancer and in chronic pancreatitis, suggesting the involvement of EGFR signaling cascade in both neoplasia and reactive hyperplasia of pancreatic ductal epithelium. However, EGF was not expressed in these cases. Thus, we hypothesize that SPINK1 is a ligand for EGFR, leading to the activation of its signaling pathway.
Methods & Results: We analyzed whether human SPINK1 protein can activate EGFR and its downstream target using 3T3 fibroblast and 4 pancreatic cancer cell lines (AsPC-1, MIA PaCa-2, PANC-1 and Capan-2). Our data demonstrated that EGFR and its downstream target were phosphorylated by SPINK1 stimulation.
Conclusions: SPINK1 exhibits growth stimulating activity to these cell lines through EGFR/MAPK cascade, suggesting that the EGFR is the receptor for SPINK1.