Targeted disruption of S100P suppresses tumor cell growth by down-regulation of cyclin D1 and CDK2 in human hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The number of cases of HCC has continued to increase in recent decades. Previous studies have suggested that S100P, a member of the S100P calcium-binding protein family, is aberrantly regulated in several malignant neoplasms. However, the underlying molecular mechanisms of the dysregulation of S100P remain to be elucidated. To investigate biological effects of S100P on hepatocarcinogenesis, aberrant expression of S100P was investigated by immunohistochemistry (IHC), Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) in HCC tissues and cell lines. Endogenous expression of S100P was disrupted by the RNA interference-mediated protein knockdown method in the human Hep3B liver cancer cell line. Then, cell growth and cellular apoptosis were compared with control siRNA transfectants. The effects of S100P-silencing on the major components of cell cycle regulation were assessed by Western blot analysis. As results, elevated levels of S100P were observed in the HCC tissues compared to the corresponding normal tissues. Targeted disruption of S100P suppressed cell growth and augmented cellular apoptosis. In addition, inhibition of S100P resulted in the down-regulation of cyclinD1 and CDK2. In conclusion, this study showed over-expression of S100P in HCC. The aberrant regulation of S100P in HCC might activate cyclin D1 and CDK expression and contribute to the mitogenic potential of tumor cells during HCC carcinogenesis. These findings provide information that suggests new therapeutic strategies for the treatment of liver cancer.
Kim
Jeong Kyu
JK
Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Jung
Kwang Hwa
KH
Noh
Ji Heon
JH
Eun
Jung Woo
JW
Bae
Hyun Jin
HJ
Xie
Hong Jian
HJ
Ahn
Young Min
YM
Ryu
Jae Chun
JC
Park
Won Sang
WS
Lee
Jung Young
JY
Nam
Suk Woo
SW
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D009687:Nuclear Proteins; C496889:S100PBP protein, human; D019938:Cyclin D1; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2