Pancreatic Cancer is the second most common gastrointestinal malignancy and the fifth leading cause of cancer deaths in the United States. With an estimated 30,000 cases diagnosed annually, it is a highly lethal malignancy with a mortality rate greater than 90% and responds poorly to radiation and chemotherapy. New specific therapeutic targets are urgently needed to develop effective therapies. Digital Differential Display (DDD) is an in-silico method that can compare the frequencies of Expressed Sequence Tags (ESTs) between normal and tumor expression libraries. We identified a novel gene MGC10471 by using DDD that is overexpressed in pancreatic tumor libraries as compared with libraries from normal tissues. Genes that are overexpressed in cancers are often important for cell survival and tumor growth. MGC10471 mRNA expression has been shown to be induced by serum stimulation. Also, MGC10471 amino acid sequence contains binding and phosphorylation sites for two oncogenic kinases, Polo like kinase (Plkl) and Protein kinase B (AKT). Our central hypothesis is that MGC10471 may have a role in tumor progression. The goals of this proposal are to characterize the novel gene MGC10471 and study its role in pancreatic cancer.
The specific aims of this proposal are: 1. To determine the effect of MGC10471 on in vitro growth, and cell survival in response to cytotoxic stimuli by overexpressing and depleting MGC 10471 protein in pancreatic cancer cell lines 2. (a) To determine the role of MGC10471 in cell signaling by identifying the downstream effectors using microarrays. (b) We will test the hypothesis, based on bioinformatics leads that """"""""MGC10471 protein could bind and act as substrate for Plkl and/or AKT"""""""". Our long-term goal is to develop MGC 10471 as a novel therapeutic target in pancreatic cancer.
| Dorsey, Charles H; Cousin, Carolyn E; Lewis, Fred A et al. (2002) Ultrastructure of the Schistosoma mansoni cercaria. Micron 33:279-323 |
