Collaborative Award: Unfolded protein response in NETs

Year: 2015
Institution: San Francisco (Contracts & Grants), The Regents of the University of California
Country: United States
State: CA
Award Type: NETRF GRANTS 2005-2017
NET Type: Pancreas
Science Type: Translational

General Description

Dr. Chung’s research focuses on determining whether there are unique protein expression patterns in gastrointestinal (GI) neuroendocrine tumors that can provide novel insights into disease pathogenesis. Dr. Chung is performing proteomic analysis of carcinoid to address this critical gap in scientific knowledge. Analysis of the proteome is inherently more challenging than that of the genome, but the potential insights that can be gained are unobtainable through a gene-based approach. Proteomic technologies have also matured so that comprehensive and meaningful analyses of tumor samples are now realistic. GI neuroendocrine tumors lend themselves to this type of proteomic analysis because they are rather homogeneous in terms of their cellular composition. 

Dr. Chung’s research will define the proteomic profile of neuroendocrine tumors relative to normal tissue. Dr. Chung will also address several other questions, such as whether there may be protein markers that can distinguish benign versus malignant disease, predict natural history, or serve as novel therapeutic targets. Dr. Chung is also undertaking a gene array expression strategy. The combination of complementary data sets from Dr. Chung’s DNA microarray and proteomic approaches will be a powerful one.

Results

This proteomic-based project identified the role of two key proteins, the PDGF receptor and HOXC6, as novel targets in NETs. Dr. Chung’s laboratory discovered that a protein called HoxC6 was dramatically up-regulated in gastrointestinal neuroendocrine tumors and that expression was low in normal tissues, indicating that the HoxC6 gene may play a role in tumor development. Further studies revealed that HoxC6 is an important regulator of a signaling pathway that had not previously been implicated in neuroendocrine tumors.

Publications

Modlin IM, Moss SF, Chung DC, Jensen RT, Snyderwine E. Priorities for Improving the Management of Gastroenteropancreatic Neuroendocrine Tumors. J Natl Cancer Inst. 2008 Sep 17; 100(18): 1282–1289.
Published online 2008 Sep 17. doi: 10.1093/jnci/djn275

Fujiki K1, Duerr EM, Kikuchi H, Ng A, Xavier RJ, Mizukami Y, Imamura T, Kulke MH, Chung DC. Hoxc6 is overexpressed in gastrointestinal carcinoids and interacts with JunD to regulate tumor growth. Gastroenterology. 2008 Sep;135(3):907-16, 916.e1-2. doi: 10.1053/j.gastro.2008.06.034. Epub 2008 Jul 23.

Duerr EM, Mizukami Y, Ng A, Xavier RJ, Kikuchi H, Deshpande V, Warshaw AL, Glickman J, Kulke MH, Chung DC. Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocr Relat Cancer. 2008 Mar;15(1):243-56. doi: 10.1677/ERC-07-0194.