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Cripto, a member of the epidermal growth factor family, is over‐expressed in human pancreatic cancer and chronic pancreatitis
Author(s) -
Friess Helmut,
Yamanaka Yoichiro,
Büchler Markus,
Kobrin Michael S.,
Tahara Eiichi,
Korc Murray
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910560511
Subject(s) - pancreatic cancer , ductal cells , pancreas , pancreatitis , cancer , cancer research , epidermal growth factor , biology , pancreatic disease , northern blot , tgf alpha , endocrinology , pathology , transforming growth factor , epidermal growth factor receptor , medicine , gene expression , receptor , gene , biochemistry
Cripto is a 188 amino‐acid protein containing a central segment that shares amino‐acid sequence homology with epidermal growth factor (EGF) and transforming growth factor alpha (TGF‐α). The EGF receptor, EGF and TGF‐α are expressed in the normal human pancreas, and are over‐expressed in human pancreatic cancer. Therefore, in the present study we sought to determine whether 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 fibrosis similar to that observed in pancreatic cancer, we also examined cripto expression in pancreatic tissues from patients with CP. In the normal pancreas, cripto immunoreactivity was found at moderate levels in 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 present in acinar and ductal cells adjacent to the cancer cells, and in many ductal and atrophic acinar cells in the CP samples. Northern blot analysis revealed a marked increase in cripto mRNA levels in the cancer and CP samples. By densitometry, there was a 11 ‐ and 4‐fold increase in cripto mRNA levels in pancreatic cancer and CP respectively. Southern 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.