Apoptosis and expression of the Bcl-2 family of proteins and P53 in human pancreatic ductal adenocarcinoma.
OBJECTIVE
The purpose of this study was to clarify the association between P53 and the Bcl-2 family (Bcl-2, Bax, Bcl-xL, Bcl-xS) expression and apoptosis in pancreatic ductal adenocarcinoma (PDAC).


METHODS
A total of 70 patients with PDAC were studied. The expression of P53 protein in PDAC was assessed using the immunohistochemical method, which categorized the PDAC patients into two groups: group 1: 36 cases with immunonegative P53(-), and group 2: 34 cases with immunopositive P53(+). The expression of Bcl-2, Bax, Bcl-xL, and Bcl-xS in the 70 PDAC cases was detected by immunohistochemical and Western blotting methods. The apoptotic index (AI) was also measured in these samples by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The relation between P53 and the Bcl-2 protein family and apoptosis was then evaluated.


RESULTS
Bcl-2 and Bcl-xS expression was significantly associated with P53 (p < 0.05). No clear associations were found among P53, Bax and Bcl-xL expression (p > 0.05). The AI of groups 1 and 2 was 12.1 ± 2.47 and 8.1 ± 1.48, respectively (p = 0.023). There was no relationship between AI and Bcl-2, Bax, Bcl-xL and Bcl-xS expression (p > 0.05, respectively). Bcl-2/Bax ratio was significantly associated with AI (p < 0.01).


CONCLUSIONS
Bcl-2 and Bcl-xS represent significant anti- and proapoptotic proteins, respectively, modulated through a P53-dependent pathway in PDAC, and P53 modulated apoptosis mainly through Bcl-2/Bax ratio.
Department of General Surgery, Affiliated Hospital of Medical College, QingDao University, QingDao, ShanDong Province, People’s Republic of China.
Dong
D
Chen
Xuefeng
X
Zheng
Dalu
D
Kang
Bomin
B
Yan
Xiaoyi
X
Liu
Yuan
Y
Gao
Kejun
K
Zhang
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D017209:Apoptosis; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology*; D016009:Chi-Square Distribution; D019254:Genes, bcl-2 / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein