Pancreatic cancer is a devastating disease that occurs in nearly 30,000 Americans annually and is the fifth leading cause of cancer-related deaths in the United States. From the time of diagnosis the median survival for patients with pancreatic cancer is approximately 3 to 6 months. The reasons for this aggressive behavior include the inability to detect patients with this malignancy at early stages, resistance to standard chemotherapy, and a poor understanding of the mechanisms involved in growth regulation of pancreatic cancer. Peptides of the CCK-gastrin family have been shown to stimulate growth of pancreatic cancer through selective CCK-like receptors and blockade of this receptor with antagonists results in growth indeed be unique. Unlike many other cultured cells, pancreatic cancer cells thrive readily in growth media deprived of serum since they produce gastrin, which in turn regulates growth of this cancer in a tonic and autocrine fashion. Based upon her preliminary findings, she puts forth the hypothesis that the growth of human pancreatic cancer is mediated through a unique CCK-like receptor, dependent upon gastrin and/or CCK, and that deprivation of these peptides will inhibit growth of this malignancy. In order to test this hypothesis it is proposed to 1) determine the biological form of gastrin and /or CCK involved in pancreatic cancer growth by performing growth studies, Reverse-phase HPLC, and radioimmunoassay, 2) characterize the differences between peptides and receptor expression of human pancreas cancer tissues and normal pancreas tissues, 3) study the functional significance of CCK/gastrin gene expression by stable transfections of these peptides into pancreatic cancer cells, 4) characterize the molecular properties of the receptor by cloning and sequencing the receptor, and 5) examine the functional significance of the unique CCK-like receptor by examining it's over and under expression in stable transfected cell lines. These studies are part of the team's long-term goal to understand the mechanisms involved in the biology of human pancreatic cancer, and contribute to the treatment and early detection of this malignancy.
| Smith, Jill P; Verderame, Michael F; Ballard, Elizabeth N et al. (2004) Functional significance of gastrin gene expression in human cancer cells. Regul Pept 117:167-73 |
| Smith, Jill P; Verderame, Michael F; McLaughlin, Patricia et al. (2002) Characterization of the CCK-C (cancer) receptor in human pancreatic cancer. Int J Mol Med 10:689-94 |
