MSX2, a member of the homeobox genes family, is demonstrated to be the downstream target for ras signaling pathway and is expressed in a variety of carcinoma cells, suggesting its relevance to the development of ductal pancreatic tumors since pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary-mucinous neoplasia (IPMN) harbor frequent K-ras gene mutations. Recent studies revealed the roles of MSX2 in the development of carcinoma of various origins including pancreas. Among gastrointestinal tumors, PDAC is one of the most malignant. PDAC progresses rapidly to develop metastatic lesions, frequently by the time of diagnosis, and these tumors are usually resistant to conventional chemotherapy and radiation therapy. The molecular mechanisms regulating the aggressive behavior of PDAC still remain to be clarified. On the other hand, IPMN of the pancreas is distinct from PDAC because of its intraductal growth in the main pancreatic duct or secondary branches with rare invasion and metastasis to distant organs. However, recent evidence indicated that once IPMN showed stromal invasion, it progresses like PDAC. Therefore, it is important to determin how IPMN progresses to malignant phenotype. In this review, we focus on the involvement of MSX2 in the enhancement of malignant behavior in PDAC and IPMN, and further highlight the clinical approach to differentiate PDAC from chronic pancreatitis by evaluating MSX2 expression level.
Keywords: pancreatic ductal adenocarcinoma, intraductal papillary-mucinous neoplasm of the pancreas, cancer development, MSX2, homeobox gene
Citation: Satoh K, Hamada S and Shimosegawa T (2012) MSX2 in pancreatic tumor development and its clinical application for the diagnosis of pancreatic ductal adenocarcinoma. Front. Physio. 3:430. doi: 10.3389/fphys.2012.00430
Received: 20 August 2012; Accepted: 24 October 2012;
Published online: 14 November 2012.
Edited by:Atsushi Masamune, Tohoku University Graduate School of Medicine, Japan
Reviewed by:Charles Wang, City of Hope National Medical Center/Beckman Research Institute, USA
Copyright © 2012 Satoh, Hamada and Shimosegawa. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Kennichi Satoh, Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, 47-1 Nodayama, Medeshima-Shiote, Natori, Miyagi 981-1293, Japan. e-mail: firstname.lastname@example.org