Research corner
New research on sonic hedgehog pathway
Dr. Brian Lewis's paper in the Proceedings of the National Academy of Sciences examines a key mechanism in the growth of pancreatic cancer. This research has been supported by the Pancreatic Cancer Alliance. Sonic hedgehog acts at multiple stages during pancreatic tumorigenesis Abstract: Activation of sonic hedgehog (Shh) signaling occurs in the majority of pancreatic ductal adenocarcinomas. Here we investigate the mechanisms by which Shh contributes to pancreatic tumorigenesis. We find that Shh expression enhances proliferation of pancreatic duct epithelial cells, potentially through the transcriptional regulation of the cell cycle regulators cyclin D1 and p21. We further show that Shh protects pancreatic duct epithelial cells from apoptosis through the activation of phosphatidylinositol 3-kinase signaling and the stabilization of Bcl-2 and Bcl-XL. Significantly, Shh also cooperates with activated K-Ras to promote pancreatic tumor development. Finally, Shh signaling enhances K-Ras-induced pancreatic tumorigenesis by reducing the dependence of tumor cells on the sustained activation of the MAPK and phosphatidylinositol 3-kinase/Akt/mTOR signaling pathways. Thus, our data suggest that Shh signaling contributes to tumor initiation in the pancreas through at least two mechanisms and additionally enhances tumor cell resistance to therapeutic intervention. Collectively, our findings demonstrate crucial roles for Shh signaling in multiple stages of pancreatic carcinogenesis.
>> Earlier article: Hedgehog signaling and pancreatic cancer, Dario C. Altieri, MDPancreatic Cancer Alliance Scholar
In 2006, Dr. Jennifer F. Tseng (left)
was appointed the first Pancreatic Cancer Alliance Scholar, funded in part by the Pancreatic Cancer Alliance. This has enabled Dr. Tseng, a surgeon, to concentrate on pancreatic cancer and building the pancreatic cancer treatment and research program at UMass.
She heads the UMass Surgical Outcomes Analysis & Research (SOAR) Group at UMass. SOAR's overall goal is to perform patient-oriented research to improve survival and quality of life for patients with pancreatic cancer, by using national databases, institutional databases, and internet-based tools.Since the only cures for pancreatic cancer include pancreatic surgery, but pancreatic surgery remains complex, with a major risk of death or complication, one focus of the team's research is to identify factors that can decrease the risk of death and/or major complication after pancreatic surgery. Another area of investigation is whether chemotherapy and radiation before removal of pancreatic cancer ("neoadjuvant approach") is better than traditional (surgery-first or "adjuvant") strategies. Finally, the team is in the process of developing databases where clinical information about patients including family history, symptoms, lab studies, Xrays, and treatment, can be linked to information about specific genes and proteins present in these patients and in their tumors. These links will help us understand individual risk for pancreatic cancer, and eventually, to individualize and optimize treatment strategies for patients with and at risk for pancreatic cancer. >> News story: New team's focus: pancreatic cancer; UMass Center names scholar
>> News story: UMass asst. prof wins $150,000 to do research
Other 2006 UMass research highlights
Craig C. Mello, PhD2006 Nobel Prize in Physiology or Medicine, co-recipient for discovery of RNAi
>> News story: Dr. Mello is Nobel winner; Prize won for RNAi discovery Jennifer Tseng, MD
Pancreatic Cancer Alliance Scholar 2006 PanCAN-ASCO Samuel Stroum Young Investigator Award, Development of a malignancy prediction rule for cystic lesions of the pancreas
Howard Hughes Physician-Scientist Early Career Award, Development of a Malignancy Prediction Rule for Cystic Lesions of the Pancreas Brian Lewis, PhD
National Institutes of Health Grant, A Flexible Somatic and Sporadic Mouse Model for Pancreatic Ductal Adenocarcinoma
2006 PanCAN-AACR Career Development Award, Pancreatic Tumor Induction by Activated Notch Signaling
Dr. Lewis uses an imaging system funded by the Alliance in his work Ashok Saluja, MD
National Institutes of Health Grant, Heat Shock Proteins and Pancreatitis
National Institutes of Health Grant, Pathophysiology of Arginine-Induced Pancreatitis in Mice Phoebe Phillips, MD
Thomas Anthony Pappas Charitable Foundation Inc. Grant, HSP70 and survival of transformed pancreatic cells
Earlier article
Hedgehog signaling and pancreatic cancerBy Dario C. Altieri, MD
Professor and Chair of Cancer Biology, University of Massachusetts Medical School
Director, UMass Memorial Cancer Center
