Introduction of G1 phase arrest in Human Hepatocellular carcinoma cells (HHCC) by APMCF1 gene transfection through the down-regulation of TIMP3 and up-regulation of the CDK inhibitors p21.
We previously found that there was up-regulation of APMCF1 expression in apoptotic MCF-7 cells. Moreover, bioinformatics analysis has found that APMCF1 molecules had similar size and structure with molecules which belong to small G-protein superfamily. We presume that APMCF1 plays certain biological role in the regulation of cell proliferation and apoptosis. In this study, we first detected the expression pattern of APMCF1 in human hepatocellular carcinoma cell line and find no expression in Human Hepatocellular carcinoma cells (HHCC) and enhanced expression in HepG2 cells. Expression of liposome-mediated ectogenic APMCF1 induced inhibition of HHCC growth and cell cycle, and RNAi inhibited APMCF1 expression and promoted HepG2 cell growth. Results of cell cycle gene chips analysis showed up-regulation of p21 expression and down-regulation of TIMP3 in HHCC cells expressing ectogenic APMCF1, indicating that APMCF1 participates at least partially in cell cycle regulation through regulating genes such as p21 and TIMP3.
Li
Qinlong
Q
Department of Pathology, State Key Laboratory of GI Cancer Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
Yan
Wei
W
Cheng
Shengquan
S
Guo
Shuangping
S
Wang
Wenyong
W
Zhang
Zhipei
Z
Wang
Li
L
Zhang
Jing
J
Wang
Wenliang
W
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D050759:Cyclin-Dependent Kinase Inhibitor p21; D011518:Proto-Oncogene Proteins; C449560:SRPRB protein, human; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019204:GTP-Binding Proteins