Reduced expression of molecules of the cadherin/catenin complex in the transition from colorectal adenoma to carcinoma.
E-cadherin is crucial to the intercellular adherens junctions which are involved in the organisation and maintenance of epithelial structure and suppression of tumour invasion. E-cadherin is associated with the actin cytoskeleton via cytoplasmic proteins, including alpha-, beta- and gamma-catenins, which together form the cadherin/catenin complex. To evaluate changes of the molecules of the cadherin/catenin complex in colorectal carcinogenesis, seventy-four sporadic adenomas, samples of histologically normal epithelium adjacent to 65 adenomas, and 52 carcinomas arising in adenomas were investigated by immunohistochemistry. All normal epithelial cells showed a uniform membranous staining pattern for E-cadherin, alpha-, beta-, and gamma-catenin. Decreased expression of all 4 proteins occurred in parallel in adenomas and carcinomas (in all cases, p < 10(-5). Decreased expression of the cadherin/catenin complex in adenomas was associated with increasing severity of dysplasia (p < 0.001, for E-cadherin, alpha-, and gamma-catenin, p < 0.005 for beta-catenin). Carcinomas displayed significantly reduced expression of the cadherin/catenin complex compared with their associated adenomas (all p < 0.001). The results directly confirm that colorectal tumour progression and invasion is associated with disruption of the cadherin/catenin complex and suggest that the genetic changes and transcriptional modulation of catenins underlying this progression may affect all members of the complex.
Hao
X
X
Academic Department of Pathology, St Mark's Hospital, Harrow, U.K.
Palazzo
J P
JP
Ilyas
M
M
Tomlinson
I
I
Talbot
I C
IC
D000236:Adenoma / Q000473:pathology*; D015820:Cadherins / Q000032:analysis* / Q000096:biosynthesis; D002277:Carcinoma / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000096:biosynthesis; D051180:Desmoplakins; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin