Prognostic significance of Beclin 1-dependent apoptotic activity in hepatocellular carcinoma.
Autophagy is believed to be important in tumorigenesis and tumor progression. However, the role of autophagy in hepatocellular carcinoma (HCC), and especially the prognostic value of autophagic proteins, has not been investigated. Our studies described here show decreased basal expression of autophagic genes and their corresponding autophagic activity under conditions of starvation in HCC cell lines, and the autophagy defect correlated well with the highly malignant phenotype of HCC. In addition, in a tissue microarray study of HCC patients who underwent resection, the expression of the autophagy-related protein Beclin 1 was extremely low in tumors, where Beclin 1 could predict the prognosis of HCC patients only in a Bcl-X(L)-positive expression background. Based on our results, we propose that autophagy defects that synergize with altered apoptotic activity might facilitate tumor progression and poor prognosis of HCC, due to the fact that autophagy may interact with apoptosis in the regulation of HCC.
Shi
Ying-Hong
YH
Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 180 FengLin Road, Shanghai, China.
Ding
Zhen-Bin
ZB
Zhou
Jian
J
Qiu
Shuang-Jian
SJ
Fan
Jia
J
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001343:Autophagy; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D010641:Phenotype; D011379:Prognosis; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D051020:bcl-X Protein