DESCRIPTION: The long term goal of this study is to determine the role of TGFbeta RII receptor (RII) in pancreatic cancer. Loss of response to TGFbeta appears common to pancreatic cancer, which is often caused by a loss of the RII gene expression. The hypothesis to be tested in this revised application is that the loss of RII expression is caused by ras-mediated down regulation of the gene and that lack of a functional RII receptor plays an important role in the tumorigenic properties of pancreatic cancers. The specific aims are 1) Determine the mechanism by which oncogenic ras inhibits RII expression and/or causes resistance to growth inhibition by TGFbeta, and 2) Determine the biological role of RII in tumor progression in ras-mutated pancreatic cancer cells.