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6th ESACP Congress, Heidelberg, April 7-11, 1999 |
A085
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.
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