The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-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 D1, 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 p16INK4A. Therefore, we investigated the expression profiles of nuclear beta-catenin, cyclin D1, p16INK4A, 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 D1, p16INK4A, and Ki-67. It was observed that expression of nuclear beta-catenin, cyclin D1, and p16INK4A 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 D1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D1 should be reconsidered in view of these observations.
Jung
A
A
Department of Molekulare Pathologie, Pathologisches Institut, Universität Erlangen-Nürnberg, Erlangen, Germany. andreas.jung@patho.imed.uni-erlangen.de
Schrauder
M
M
Oswald
U
U
Knoll
C
C
Sellberg
P
P
Palmqvist
R
R
Niedobitek
G
G
Brabletz
T
T
Kirchner
T
T
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D003598:Cytoskeletal Proteins; D019394:Ki-67 Antigen; D015534:Trans-Activators; D051176:beta Catenin