Survivin promotes cell proliferation in human hepatocellular carcinoma

Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC...

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Bibliographic Details
Published in:Hepatology (Baltimore, Md.) Md.), 2000-05, Vol.31 (5), p.1080-1085
Main Authors: Ito, Takeshi, Shiraki, Katsuya, Sugimoto, Kazushi, Yamanaka, Takenari, Fujikawa, Katsuhiko, Ito, Masaaki, Takase, Koujiro, Moriyama, Masami, Kawano, Hirokazu, Hayashida, Midori, Nakano, Takeshi, Suzuki, Atsushi
Format: Article
Language:English
Subjects:
Apoptosis
Biological and medical sciences
Carcinoma, Hepatocellular - etiology
Carcinoma, Hepatocellular - pathology
Cell Cycle
Cell Division
Cyclin-Dependent Kinase 4
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinases - metabolism
Cyclins - metabolism
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Inhibitor of Apoptosis Proteins
Liver Neoplasms - etiology
Liver Neoplasms - pathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Microtubule-Associated Proteins
Neoplasm Proteins
Proteins - analysis
Proteins - genetics
Proteins - physiology
Proto-Oncogene Proteins
RNA, Messenger - analysis
Tumor Cells, Cultured
Tumors
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Summary:Survivin is a recently described inhibitor of apoptosis. Because suppression of apoptosis is important for carcinogenesis and tumor growth, we investigated the expression and function of survivin in human hepatocellular carcinomas (HCCs). We have shown that 4 HCC cell lines and 7 out of 8 human HCC tissues expressed survivin messenger RNA (mRNA), whereas expression of survivin mRNA was not detected in normal liver and nontumor areas of these tissues using the reverse transcription polymerase chain reaction. Survivin was detected primarily in the nucleus by immunofluorescence staining of HCC cells. In addition, 14 of 20 (70%) HCC tissues showed positive nuclear staining for survivin, whereas nontumor tissues showed little detectable staining by immunohistochemistry. Survivin expression strongly correlated with the proliferation index but not significantly with the apoptosis index in HCC tissues. Therefore, we performed cell cycle analysis after survivin transfection and showed that overexpression of survivin resulted in a decrease in the G0 /G1 phase and an increase in the S phase in all 4 HCC cell lines. Furthermore, we have found that survivin interacted with cyclin‐dependent kinase 4 (Cdk4) and overexpression of survivin released p21WAF1/Cip1 (p21) from Cdk4. From these results, we conclude that survivin promotes cell proliferation by interacting with Cdk4 and releasing p21 from Cdk4. This may play an important role in carcinogenesis and progression of human HCCs.
ISSN:0270-9139
1527-3350
DOI:10.1053/he.2000.6496