Heterodimerization of Bcl-2 and Bcl-X(L) with Bax and Bad in colorectal cancer.
The rate of cell loss owing to apoptosis is mediated by competitive dimerization with selective pairs of cell death antagonists (Bcl-2, Bcl-X(L)) and agonists (Bax, Bad). The aim of this study was to investigate which Bcl-2 family dimers had a critical factor in colorectal cancer. We analyzed the expression of Bcl-2, Bcl-X(L), Bax, and Bad in normal-appearing mucosa and colorectal tumor tissues by Western blotting after immunoprecipitation. Compared with the ratio of Bax-Bcl-2/total Bax in normal mucosa, the ratio was significantly reduced in tumors (p = 0.02). In this series, the low ratio of Bad-Bcl-2/total Bcl-2 was associated with advanced tumor stages (p = 0.02). A reduced heterodimerization of Bax with Bcl-2 may contribute to the development of colorectal cancer. The heterodimerization of Bad with Bcl-2 may be repressed in advanced tumor tissues, and may contribute to tumor growth in colorectal cancer.
Hattori
T
T
Department of Gastroenterology, Fujigaoka Hospital, Showa University, Yokohama, Japan. thattori@tka.att.ne.jp
Ookawa
N
N
Fujita
R
R
Fukuchi
K
K
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D019281:Dimerization; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein
C494819:BAD protein, human; C494826:BAX protein, human; C494811:BCL2L1 protein, human; D002352:Carrier Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein