The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells  

作　　者：MENG SEN LI, PING FENG LI, FBI YI YANG, SHI PENG HE, Guo GUANG DU, GANG LI1 Department of Biochemistry and Molecular Biology, 2 Department of Biophysics, Health Science Center, Peking University, Beijing 100083, China 

出　　处：《Cell Research》2002年第2期151-156,共6页细胞研究（英文版）

基　　金：This work was supported by National NaturalScience Fundation of China(No.39760077).

摘　　要：AIM: The existence and properties of alpha-fetoprotein (AFP) receptor on the surface of NIH 3T3 cells and the effects of AFP on cellular signal transduction pathway were investigated. METHODS: The effect of AFP on the proliferation of NIH 3T3 cells was measured by incorporation of 3H-TdR. Receptor-binding assay of 125I-AFP was performed to detect the properties of AFP receptor in NIH 3T3 cells. The influences of AFP on the [cAMP]i and the activities of protein kinase A (PKA) were determined. Western blot was used to detect the change of K-ras P21 protein expression. RESULTS: The proliferation of NIH 3T3 cells treated with 0-80 mg/L of AFP was significantly enhanced. The Scatchard analysis indicated that there were two classes of binding sites with KD of 2.722 x 10(-9)M (Bmax=12810 sites per cell) and 8.931 x 10(-8)M (Bmax=119700 sites per cell) respectively. In the presence of AFP (20 mg/L), the content of cAMP and activities of PKA were significantly elevated . The level of K-ras P21 protein was upregulated by AFP at the concentration of 20 mg/L. The monoclonal antibody against AFP could reverse the effects of AFP on the cAMP content, PKA activity and the expression of K-ras p21 gene. CONCLUSION: The effect of AFP on the cell proliferation was achieved by binding its receptor to trigger the signal transduction pathway of cAMP-PKA and alter the expression of K- ras p21 gene.

关 键 词：3T3 Cells Animals Cell Division Cyclic AMP Cyclic AMP-Dependent Protein Kinases Dose-Response Relationship  Drug Humans Mice Receptors  Peptide Research Support  Non-U.S. Gov't Signal Transduction Time Factors ALPHA-FETOPROTEINS 

分 类 号：Q24[生物学—细胞生物学]