alpha-1,3-Fucosyltransferase-VII stimulates the growth of hepatocarcinoma cells via the cyclin-dependent kinase inhibitor p27Kip1.
After the transfection of alpha-1,3-fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the protein expression of some cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDIs) p16INK4 and p21waf1/Cip1 were unchanged. However, CDI p27Kip1 protein, both the total amount and the amount that bound to CDK2, but not its mRNA, was significantly reduced. The de-inhibited CDK2 stimulated the phosphorylation of retinoblastoma (Rb) protein and facilitated the G1/S transition and growth rate of the cells. The decrease of p27Kip1 protein, the increase of CDK2 activity and Rb phosphorylation, as well as the cell growth and percentage of S phase cells were correlated to the increased amount of cell surface sialyl Lewis X (SLe(x)) antigen in cells with different alpha-1,3-FucT-VII expression. The reduction in p27Kip1 and the difference in its expression among different transfected cells were blocked by the SLe(x) antibody KM93 in a dose-dependent manner, indicating that p27Kip1 expression was influenced by alpha-1,3-FucT-VII and its product SLe(x). The MEK/MAPK signaling pathway was more important than the PI-3K pathway in the regulation of p27Kip1 expression.
Wang
Q Y
QY
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Guo
P
P
Duan
L L
LL
Shen
Z H
ZH
Chen
H L
HL
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase