CRIPTO, A MEMBER OF THE EPIDERMAL GROWTH-FACTOR FAMILY, IS OVER-EXPRESSED IN HUMAN PANCREATIC-CANCER AND CHRONIC-PANCREATITIS

Cripto is a 188 amino-acid protein containing a central segment that s hares amino-acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha). The EGF receptor, EG F and TGF-alpha are expressed in the normal human pancreas, and are ov er-expressed in human pancreatic cancer. Therefore, in the present stu dy we sought to determine wheather cripto is found in the normal human pancreas and whether its expression is altered in pancreatic cancer. Because chronic pancreatitis (CP) is associated with interstitial fibr osis similar to that observed in pancreatic cancer, we also examined c ripto expression in pancreatic tissues from patients with CP. In the n ormal pancreas, cripto immunoreactivity was found at moderate levels i n most ductal cells and was present very faintly in a rare acinar cell . In 26 of 58 pancreatic cancers, cripto immunoreactivity was present in many cancer cells. Its presence was associated with advanced tumor stage, but not with shorter post-operative survival. Cripto was also p resent in acinar and ductal cells adjacent to the cancer cells, and in many ductal and atrophic acinar cells in the CP samples. Northern blo t analysis revealed a marked increase in cripto mRNA levels in the can cer and CP samples. By densitometry, there was a 11- and 4-fold increa se in cripto mRNA levels in pancreatic cancer and CP respectively. Sou thern blot analysis did not reveal an increase in gene copies encoding cripto either in cancer or in CP. These findings indicate that cripto expression may contribute to disease progression in pancreatic cancer , and implicate cripto in the histopathological alterations that occur in the pancreas both in cancer and in CP. (C) 1994 Wiley-Liss, Inc.