Research On The FGF-2 And TPA-induced MMP-9 Secretion Mechanism In Breast Cancer Cell MCF-7

Previous Studies has demonstrated matrix metalloproteinases (MMPs) play an important role in multiple pathological process,such as cancer metastasis, inflammation, cancer cell proliferation,by hydrolyzing the extracellular matrix.By this way, MMPs regulate the homeostasis of ECM's disperse and recombination. As known, breast cancer is one of the most common tumor diseases. Cancer metastasis and pervasion are also involved in the process of breast cancer. Here, we investigated the effect of fibroblast growth factor-2 (FGF-2) and 12-O-tetradecanoylphorbol-13-acetate (TPA) on the secretion of type IV collagenases (MMP-9) in breast cancer MCF-7 cells. As shown by gelatin zymography, both FGF-2 and TPA stimulated the secretion of MMP-9 in MCF-7 cells while TPA stimulated more than FGF-2.However, in MCF-7-Ras (Ras overexpresion) and MCF-7-Ras/N17 (Ras dominant negative), both the effects of TPA and FGF-2 were blocked nearly. Additionally, in the MCF-7-Antisense PTPL1/FAP-1 (PTPL1/FAP-1 silenced- expression), the effect of TPA was enhanced while FGF-2 still kept its stimulation effect in the same level as in the MCF-7 cell. These foundings has raised the possibility that Ras activation concentration contributes to the invasive characteristic of MCF-7. One decent concentration of Ras is indispensable for the secretion of MMP-9 in the MCF-7.Another conclusion which has been probably proved is PTPL1/FAP-1 took part in the process of breast cancer cell apoptosis by partly inhibition of breast cancer cell metastasis since there are the stronger survive abilities to offset the OH-tamoxifen-induced cell apoptosis effect in the MCF-7-Antisense PTPL1/FAP-1.