Overexpression of epidermal growth factor receptor in Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is characterized by gastrointestinal hamartomatous p olyposis, mucocutaneous pigmentation, and a predisposition to cancer. The e tiology of this syndrome is unknown. We investigated the expression of epid ermal growth factor receptor (EGFr), transforming growth factor-alpha (TGF- alpha), transforming growth factor-beta(1), (TGF-beta(1)) and transforming growth factor-beta receptor (TGF-beta RII) between normal and Peutz-Jeghers small bowel tissues, In addition, immunoprecipitation by phosphotyrosine a ntibodies followed by EGFr western blotting was measured and compared betwe en a Peutz-Jeghers hamartoma and normal duodenal tissue. EGFr expression wa s increased 2.5-fold in normal and hamartomatous tissue of Peutz-Jeghers pa tients compared to normal small bowel tissue. In Peutz-Jeghers tissues, the major EGFr immunoreactive band was increased size from 170 to approximatel y 200 kDa, Using an antibody specific for activated EGFr, this larger size band was predominant in Peutz-Jeghers tissue. Immunoprecipitation of a hama rtoma by a phosphotyrosine specific antibody followed by western blotting f ur EGFr demonstrated this 200-kDa band. Expression of TGF-alpha, TGF-beta 1 , TGF-beta RII was not significantly different between normal and Peutz-Jeg hers tissues, In conclusion, EGFr was overexpressed in normal and hamartoma tous small bowel tissue of Peutz-Jeghers patients, which suggests that EGFr in Peutz-Jeghers tissue is persistently activated or highly stimulated by endogenous ligands and also suggests a possible role for EGFr in the pathog enesis of Peutz-Jeghers syndrome.