Objective To explore the molecular mechanism of anti-angiogensis in HER-2/neu-overexpressing breast cancer by genistein.
Methods HER-2/neu negative expression breast cancer MCF-7 cells were transfected with HER-2/neu to establish HER-2/neu-overexpressing MCF-7 cells(named MCF-7/HER-2).Western blot, immunoprecipitate, reverse transcription-polymerase chain reaction(RT-PCR)and kinase activity analysis technicals were used to observe the expression of uPA and the protein phosphorylation of HER-2/neu receptor and the activity of protein tyrosine kinase(PTK)in MCF-7/HER-2 cells treated by genistein for 24, 48, 72 h.
Results The expression of uPA was significantly higher in MCF-7/Her-2 cells than that in MCF-7 cells both in mRNA and protein.The expression of uPA mRNA and the protein, phosphorylation of HER-2/neu receptor and the activity of PTK also significantly were decreased after treated with 5×10-5 mol/L genistein, which had a time-dependence.
Conclusion Genistein could down-regulate the activity of PTK and the protein phosphorylation of HER-2/neu receptor, and inhibit the expression of uPA in breast cancer cells, which is possible one of the molecular mechanisms of genistein anti-angiogenesis in breast cancer.