Expression of Bcl-2 family modulated through p53-dependent pathway in human hepatocellular carcinoma.
The biological behavior of hepatocellular carcinoma (HCC) is, in part, relevant to apoptosis. A systematic investigation of the apoptosis-related Bcl-2 family modulated by p53 in HCC is lacking. A total of 22 HCC patients were studied. The expression of p53 protein in HCC was assessed using the immunohistochemical method, which categorized the HCC patients into two groups: group 1, with immunonegative p53 (N = 7); and group 2, with immunopositive p53 (N = 15). The expression of p53, p21, Bcl-2, Bax, Bcl-xL, and Bcl-xS in the 22 HCC cases detected by western bioting was quantified with a densitometer. The apoptosis of the 22 HCC cases was determined by terminal deoxynucleotidyltransferase-mediated UTP end-labeling (TUNEL). We found that Bcl-2 was remarkably up-regulated in group 2 (14 of 15), but was down-regulated in group 1 (5 of 7). Bax was up-regulated in both group 1 (6 of 7) and group 2 (13 of 15). Bcl-xL was up-regulated in both group 1 (5 of 7) and group 2 (9 of 15). Bcl-xS was remarkably down-regulated in group 2 (14 of 15) compared to group 1 (4 of 7). The apoptosis indexes of groups 1 and 2 were 0.82 +/- 0.26% and 0.33 +/- 0.17%, respectively (P = 0.023). The long-term survival of group 1 was superior to that of group 2 (log-rank test, P = 0.001). In conclusion, Bcl-2 and Bcl-xS represented the most significant anti- and proapoptotic proteins, respectively, modulated through a p53-dependent pathway in HCC.
Chiu
Cheng-Tang
CT
Department of Gastroenterology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
Yeh
Ta-Sen
TS
Hsu
Jui-Chen
JC
Chen
Mün-Fu
MF
D017209:Apoptosis / Q000502:physiology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000473:pathology*; D015536:Down-Regulation; D006801:Humans; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology; D008113:Liver Neoplasms / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein