Expression of bcl-2, bax, and bcl-XL proteins in azoxymethane-induced rat colonic adenocarcinomas.
Using western blotting and immunochemical analysis, we investigated alterations in the expression of the apoptosis-related proteins bcl-2, bax, and bcl-X in colonic adenocarcinomas induced by subcutaneous injection of azoxymethane (AOM) (15 mg/kg body weight weekly for 2 wk) into male Sprague-Dawley rats. Expression of the apoptosis-repressor bcl-2 in the colonic tumors was significantly weaker (0.6-fold) than that in adjacent non-neoplastic mucosa. The expression of bax protein, an apoptosis accelerator, was significantly stronger (7.33-fold) in all the tumors than in the non-tumoral mucosa. bcl-XL protein, which functions as a repressor of apoptosis, was significantly upregulated (3.23-fold) in all the tumors when compared with the non-neoplastic mucosa. There was no significant difference between the expression of these proteins in the non-neoplastic mucosa of the AOM-treated rats and in the normal mucosa of saline-treated control rats. As determined by immunohistochemical analysis, the tumor cells had more bax and bcl-X protein. These findings indicate that the regulation of the apoptosis-related proteins bcl-2, bax, and bcl-XL was altered in the AOM-induced colonic neoplastic tissue. In terms of resistance to apoptosis, elevated levels bcl-XL protein may have considerable meaning in this experimental model as well as in human colorectal cancer.
Hirose
Y
Y
First Department of Pathology, Gifu University School of Medicine, Japan.
Yoshimi
N
N
Suzui
M
M
Kawabata
K
K
Tanaka
T
T
Mori
H
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001397:Azoxymethane; D015153:Blotting, Western; D002273:Carcinogens; D003106:Colon / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D002273:Carcinogens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D001397:Azoxymethane