epidermal-growth-factor and Pancreatitis--Chronic

Serine protease inhibitor Kazal type 1 (SPINK1) was originally identified as a trypsin inhibitor by Kazal et al. in 1948. SPINK1 is strongly elevated in pancreatitis and the elevation correlates with the severity of disease. In 2000, mutations in the SPINK1 gene were shown to be associated with chronic pancreatitis. Since then, there have been many reports on association between mutations in the SPINK1 genes and patients with pancreatitis. In 1982, SPINK1 was shown to be identical to tumor associated trypsin inhibitor (TATI). In addition, sequence similarities were detected between human epidermal growth factor (EGF) and human SPINK1 in 1983. Actually, SPINK1 was shown to stimulate growth of several cell lines including cancer cells in 1985. Recent clinical studies showed that high levels of SPINK1 protein in serum or urine were associated with adverse outcome in various cancer types. However, there was little evidence that showed in vivo function of SPINK1. Surprisingly, mice deficient in Spink3 (a mouse homologue gene of human SPINK1) showed excessive autophagy, but not pancreatitis in the exocrine pancreas, leading to autophagic cell death. We also demonstrated that SPINK1 acts as a growth factor through EGFR signaling. These data indicate that the role of the SPINK1 is not just as a trypsin inhibitor, but also as a growth factor as well as a negative regulator of autophagy. In this review, we summarize the roles of SPINK1/Spink3 in pancreatic diseases based on the data obtained from analyses using mouse models.

Topics: Animals; Autophagy; Carrier Proteins; Epidermal Growth Factor; ErbB Receptors; Glycoproteins; Humans; Mice; Mutation; Neoplasms; Pancreatitis, Chronic; Prostatic Secretory Proteins; Signal Transduction; Stimulation, Chemical; Trypsin Inhibitor, Kazal Pancreatic

The purpose of this project was to investigate the expression and clinical significance of epidermal growth factor (EGF) and the transforming growth factor-α (TGF-α) in the occurrence and development of chronic pancreatitis and pancreatic cancer.. We recruited 31 patients with chronic pancreatitis, 42 with pancreatic cancer, and 20 with normal pancreas in our hospital. Chronic pancreatitis, pancreatic cancer, and normal pancreas expressed EGF and TGF-α mRNAs as well as EGF and TGF-α proteins.. Immunofluorescence showed that EGF and TGF-α were expressed in chronic pancreatitis and pancreatic cancer, but the expression levels for both proteins were higher in pancreatic cancer. Variance analysis indicated that the differences in the expression levels of EGF and TGF-α in chronic pancreatitis, pancreatic cancer, and normal pancreas were statistically significant. The abnormally elevated expression of EGF and TGF-α are closely associated with the occurrence and development of chronic pancreatitis and pancreatic cancer.. EGF and TGF-α have important research value as indicators to assess the progression of these conditions and provide a new basis for the clinical diagnosis.

Topics: Adult; Aged; Biomarkers; Biomarkers, Tumor; Disease Progression; Epidermal Growth Factor; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis, Chronic; Transforming Growth Factor alpha