Members of the TGF ␤ family of peptides exert antiproliferative effects and induce apoptosis in epithelial cell populations. In the exocrine pancreas, these peptides not only regulate normal cell growth, but alterations in these pathways have been associated with neoplastic transformation. Therefore, the identification of molecules that regulate exocrine pancreatic cell proliferation and apoptotic cell death in response to TGF ␤ peptides is necessary for a better understanding of normal morphogenesis as well as carcinogenesis of the pancreas. In this study,

An association exists between cigarette smoking and pancreatitis owing to alcohol. We determined whether cigarette smoking affected the course of pancreatic calcification and insufficiency in idiopathic chronic pancreatitis. Medical records were analyzed of 24 persons with early- and 42 with late-onset idiopathic chronic pancreatitis who were diagnosed between 1976 and 1982 and then followed prospectively until 1985. Smoking equaled >5 pack-years before calcification or insufficiency or last follow-up. Mean follow-up after onset of chronic pancreatitis was 27 and 13 years in early- and late-onset idiopathic chronic pancreatitis, respectively. Incidence of calcification in the two groups was 58 and 43%, respectively. In early-onset idiopathic chronic pancreatitis, smokers and nonsmokers developed calcification at a similar rate and frequency (58%). In late-onset idiopathic chronic pancreatitis, smokers developed pancreatic calcifications faster (p < 0.001) and more frequently (83 vs. 13%, p < 0.001) than nonsmokers. The association between smoking and pancreatic calcification was independent of gender, body mass index, and exocrine or endocrine insufficiency. Smoking did not affect development of exocrine or endocrine insufficiency. Cigarette smoking increases the risk of pancreatic calcification of late- but not of early-onset idiopathic chronic pancreatitis. These data support encouraging cessation of smoking in chronic pancreatitis.

The study of zinc finger proteins has revealed their potential to act as oncogenes or tumor suppressors. Here we report the molecular, biochemical, and functional characterization of KS1 (KRAB/zinc finger suppressor protein 1), a novel, ubiquitously expressed zinc finger gene initially isolated from a rat pancreas library. KS1 contains 10 C 2 H 2 zinc fingers, a KRAB-A/B motif, and an ID sequence that has been shown previously to participate in growth factor-regulated gene expression. Northern blot analysis using pancreatic cell lines demonstrates that KS1 mRNA is inducible by serum and epidermal growth factor, suggesting a role for this gene in cell growth regulation. Biochemical analysis reveals that KS1 is a nuclear protein containing two transcriptional repressor domains, R1 and R2. R1 corresponds to the KRAB-A motif, whereas R2 represents a novel sequence. Transformation assays using NIH3T3 cells demonstrate that KS1 suppresses transformation by the potent oncogenes Ha-ras, G ␣ 12, and G ␣

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