Expression of Smad proteins in human colorectal cancer

Escape from transforming growth factor-beta (TGF-beta)induced inhibition of proliferation has been observed in many tumor cells and may contribute to loss of growth control, Smad proteins have been identified as major compone nts in the intracellular signaling of TGF-beta family members, In this stud y, we examined the expression of receptor-activated, common-mediator and in hibitory Smads by immunohistochemistry in human colorectal cancers. We foun d increased expression of receptor-activated Smads in a fraction of the tum or cells, while no immunostaining for Smad2, Smad3 or Smad5 and only occasi onal staining for Smad1/8 was found in epithelial mucosa of normal colon. N o or only weak staining for receptor-activated Smads, common-mediator Smad4 and inhibitory Smads was observed in the tumor stroma, Common-mediator Sma d4 and inhibitory Smads were detected in cells of both tumor and normal tis sues. We observed a distinct pattern of Smad4 immunostaining of epithelial cells along colon crypts, with high expression in zones of terminal differe ntiation. Our data show selective up-regulation of receptor-activated Smad proteins in human colorectal cancers and suggest involvement of Smad4 in di fferentiation and apoptosis of surface epithelial cells of normal crypts. ( C) 1999 Wiley-Liss, Inc.