佛波酯PMA促进碱性成纤维细胞生长因子(bFGF)释放及机理研究

STUDY ON THE MECHANISM OF BASIC FIBROBLAST GROWTH FACTOR(bFGF)RELEASE INDUCED BY PHORBOL ESTER PMA

碱性成纤维细胞生长因子(bFGF)是一个强促有丝分裂因子和促新血管生成因子,在实体瘤的发生及转移过程中起重要作用。由于bFGF缺乏信号肽序列,人们至今无法阐明bFGF释放的详细机制。我们选用PMA处理人鼻咽癌细胞CNE-2,发现胞内bFGF表达量提高,48 h后,bFGF胞外释放量有明显增加,提示PKC可能直接参与对bFGF释放的调控作用。同时我们的结果也表明:CNE-2细胞中PMA激活的PKC-α可在体外条件下磷酸化细胞内源的bFGF(18KDa)。结果提示了CNE-2细胞内PKC-α转位激活可能磷酸化胞内bFGF底物,导致bFGF释放的增加。

Basic fibroblast growth factor (bFGF) is a strong mitogenic factor and inducer of angiogene-sis. It may play an important role in the growth of solid tumors. Whereas bFGF is known to act ex-tracellularly, the protein lacks a transient signal peptide. No defined mechanism for bFGF secretion has been characterized besides release from dead or injured cells. To explore molecular mechanism that modulates bFGF release, we treated CNE-2 cells with PMA for two days and found that the treatment increased bFGF gene expression in the cytoplasm and bFGF release significantly after 48 hours. This result suggests that protein kinase C is very likely to be involved in the bFGF release regulation. Our results have also shown that PKC-α activated by PMA in CNE-2 cells can phosphorylate bFGF(18KDa)in CNE-2 cells. The result suggests that PKC-α translo-cation and activation can phosphorylate bFGF in CNE-2 cells and increase bFGF release.