P120-CATENIN EXPRESSION IN HUMAN COLORECTAL-CANCER

Recent data suggest that p120-catenin plays a role in the regulation o f functionality of E-cadherin, a protein essential for the establishme nt and maintenance of cell-cell contacts. Since dysfunction of interce llular adhesiveness is an alteration frequently observed in colon canc er we have studied the expression and distribution of p120-catenin in human colorectal tumors. In normal colon, p120-catenin was observed in the crypt and surface epithelium; the cells showed reactivity both in the membrane and in the cytosol. Thirteen primary tumors were examine d for p120-catenin expression: they were graded as uniformly positives (t) (4); heterogeneous (+/-) (6), with a diminished expression, detec ted mainly in the cytosol; and negatives (-) (3). Although the number of tumors was low, the reduction in p120-catenin correlated with a lar ger size of the tumors (p = 0.038). Association of p120-catenin to the cytoskeleton was also determined in 5 tumors by detergent extraction and Western blot; this analysis shows that lack of reactivity in the m embrane was accompanied by absence of p120-catenin in the cytoskeleton -associated fraction. Analysis of E-cadherin was performed in order to compare the distribution of this protein and p120-catenin. Although n o complete correlation was found between the expression of both protei ns (p = 0.077), our results showed that alterations in the level or di stribution of p120-catenin were accompanied by lack of E-cadherin reac tivity in the membrane, whereas absence of p120-catenin in the cytoske leton fraction was associated with important decreases in the amount o f E-cadherin in this same fraction. These results show that alteration s in p120-catenin levels are a common event in colorectal tumors, and suggest that the distribution of this protein and E-cadherin is coordi nately regulated. (C) 1996 Wiley-Liss, Inc.