Relationship between expression of Smac and Survivin and apoptosis of primary hepatocellular carcinoma.
BACKGROUND
The second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO) was recently identified as a protein that is released from mitochondria in response to apoptotic stimuli and promotes apoptosis by antagonizing inhibitor of apoptosis proteins. Furthermore, Smac/DIABLO plays an important regulatory role in the sensitization of cancer cells to both immune- and drug-induced apoptosis. However, little is known about the clinical significance of Smac/DIABLO in various cancers including hepatocellular carcinoma (HCC). This study was undertaken to investigate the expression of Smac and Survivin and their relationship with the apoptosis in primary HCC.


METHODS
The expression of Smac and Survivin proteins was evaluated by immunohistochemistry. The mRNA expression of Smac and Survivin was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in HCC tissues of 50 patients, para-carcinoma tissues of 20 patients, and normal liver tissues of 15 patients.


RESULTS
Smac mRNA was detected by RT-PCR in HCC tissues of 21 (42.0%) of the 50 patients, para-carcinoma tissues of 19 (95.0%) of the 20 patients, and normal liver tissues of 15 (100%) of the 15 patients. Survivin mRNA was found in HCC tissues of 46 of the 50 patients, para-carcinoma tissues of 2 of the 20 patients, and normal liver tissues of 0 of 15 patients. Immunohistochemistry revealed Smac protein in HCC tissues of 20 patients (40.0%), in para-carcinoma tissues of 18 patients (90.0%), and normal liver tissues of 15 patients (100.0%). The expression of Smac was significantly different in HCC tissues and non-HCC tissues. Survivin protein was found in HCC tissues in 45 patients, para-carcinoma tissues in 2 patients, and normal liver tissues in none of the patients. The expression of Survivin was significantly different in HCC tissues and non-HCC tissues.


CONCLUSIONS
Smac inhibits apoptosis of HCC cells by suppression of Survivin, and the two genes probably form an important link in the signal pathway of HCC cells.
Bao
Shi-Ting
ST
Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China. fyyb@gdmc.edu.cn
Gui
Shui-Qing
SQ
Lin
Mu-Sheng
MS
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D051017:Apoptosis Regulatory Proteins; C107489:BIRC5 protein, human; C412403:DIABLO protein, human; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D000077022:Survivin