Objective:To explore the role of MAPKs signal transduction system in the proliferation of human mammary carcinoma cell line MCF-7 induced by Leptin. Methods:Human mammary carcinoma cell line MCF-7 was treated with different concentrations of Leptin. The proliferation of MCF-7 cells was measured by MTT assay. The expression of Ob-R mRNA was detected by RT-PCR with or without MAPKs signals blocked by their each inhibitors,SP600125,the inhibitor of JNK,and PD98059,the inhibitor of ERK.The expression of JNK,p-JNK,ERK,p-ERK was detected at different time treated with leptin by Western blot. Results:Leptin increased the proliferation of MCF-7 cells in a concentration-dependent manner. Western blotting vesults implicated that 50 ng/ml Leptin induced the activation of JNK and ERK. The expression of p-JNK was detected with 3 min after Leptin treated and at the same time rapidly reached its peak. While the ERK was activated earlier than the JNK,at the 30th second after Leptin treated. The protein content of total JNK and ERK had no significant changes. Then the proliferation activated by leptin after MAPKs signaling pathway blocked by their inhibitors was reevaluated. The results showed that after inhibiting the activities of JNK and ERK,the proliferation induced by Leptin was also attenuated. Otherwise, the level of Leptin receptor expressing on the surface of MCF-7 cells was examined,which formed an autocrine loop and facilitated the effect of Leptin. 100 ng/ml Leptin increased the Ob-R mRNA level,while blocking the MAPKs signaling pathway decreased the Ob-R mRNA level. Conclusion:It demonstrated that leptin can stimulate the proliferation of MCF-7 cells in vitro. MAPKs signal transduction system involved in the proliferation,which also regulated the expression of Ob-R,forming an autocrine loop at the local site of tumor and amplifying the leptin signaling pathway.