The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear β-catenin, cyclin D1, and p16INK4A and is a region of low proliferation

At the invasion front of well-differentiated colorectal adenocarcinomas, the oncogene beta -catenin is found in the nuclear compartment of tumor cells. Under these conditions, beta -catenin can function as a transcription factor and thus activate target genes. One of these target genes, cyclin D-1, is known to induce proliferation. However, invasion front of well-differentiated colorectal adenocarcinomas are known to be zones of low proliferation and express the cell cycle inhibitor p16 (INK4A). Therefore, we investigated the expression profiles of nuclear beta -catenin, cyclin D-1, p16(INK4A), and the Ki-67 antigen, a marker for proliferation, in serial sections of well-differentiated. colorectal adenocarcinomas. Invasion fronts with nuclear beta -catenin were compared with areas from central parts of the tumors without nuclear beta -catenin, for the expression of cyclin D-1, p16(INK4A) and Ki-67. It was observed that expression of nuclear beta -catenin, cyclin D-1, and p16(INK4A) at the invasion front are significantly correlated. Such areas exhibit low Ki-67 expression indicating a low rate of proliferation. Thus, in colorectal carcinogenesis the function of beta -catenin and its target gene cyclin D-1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D-1 should be reconsidered in view of these observations.