6th ESACP Congress, Heidelberg, April 7-11, 1999

A085
RECEPTOR-ACTIVATED Smad PROTEINS ARE UP-REGULATED IN HUMAN COLORECTAL CANCER
Korchynskyi O 1 2, Landstrom M 1, Stoika R 2, Funa K 3, Heldin CH 1, ten Dijke P 1, Souchelnytskyi S 1

1) Ludwig Institute for Cancer Research, Uppsala, Sweden, 2) Institute of Biochemistry of Natl. Acad. of Sci. of Ukraine, Lviv, Ukraine, 3) Department of Medical and Cell Biology, Gothenburg University, Gothenburg, Sweden

Escape from transforming growth factor-beta (TGF-betainduced inhibition of proliferation has been observed in many tumor cells, and may contribute to a loss of growth control. Smad proteins have been identified as major components in the intracellular signalling of TGF-beta family members. In this study we examined the expression of receptor-activated, common-mediator and inhibitory Smads by immunohistochemistry in human colorectal cancers. We found an increase of expression of receptor-activated Smad1, Smad2, Smad3 and Smad5 in tumor cells, while no immunostaining for Smad2, Smad3, Smad5, and only occasional staining for Smad1, was found in epithelial mucosae of the normal colon. No, or only weak, staining for receptor-activated Smads, common-mediator Smad4 and inhibitory Smad6 was observed in the tumor stroma. Common-mediator Smad4 and inhibitory Smad6 and Smad7 were detected in cells of both tumor and normal tissues. We observed a distinctive pattern of Smad4 immunostaining of epithelial cells along colon crypts, with high expression in zones of terminal differentiation. In conclusion, our data show selective up-regulation of receptor-activated Smad proteins in human colorectal cancers, and suggest an involvement of Smad4 in the regulation of differentiation and apoptosis of surface epithelial cells of crypts.