Desmocollin switching in colorectal cancer.
The desmocollins are members of the desmosomal cadherin family of cell-cell adhesion molecules. They are essential constituents of desmosomes, intercellular junctions that play a critical role in the maintenance of tissue integrity in epithelia and cardiac muscle. In humans, three desmocollins (Dsc1, Dsc2 and Dsc3) have been described. The desmocollins exhibit tissue-specific patterns of expression; only Dsc2 is expressed in normal colonic epithelium. We have found switching between desmocollins in sporadic colorectal adenocarcinoma with a reduction in Dsc2 protein (in 8/16 samples analysed by immunohistochemistry) being accompanied by de novo expression of Dsc1 (16/16) and Dsc3 (7/16). Similar results were obtained by western blotting of a further 16 samples. No change was found in Dsc2 mRNA, but de novo expression of Dscs 1 and 3 was accompanied by increased message levels. Loss of Dsc2 (8/19) and de novo expression of Dsc1 (11/19) and Dsc3 (6/19) was also found in colorectal adenocarcinomas on a background of colitis. The data raise the possibility that switching of desmocollins could play an important role in the development of colorectal cancer.
Khan
K
K
Division of Medical Sciences, University of Birmingham, Clinical Research Block, Queen Elizabeth Hospital, Birmingham, UK.
Hardy
R
R
Haq
A
A
Ogunbiyi
O
O
Morton
D
D
Chidgey
M
M
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003092:Colitis / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
C081560:DSC1 protein, human; C081561:DSC2 protein, human; C490356:DSC3 protein, human; D051187:Desmocollins; D012333:RNA, Messenger