MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer.

摘要: Although cell invasion is a necessary early step in cancer metastasis, its regulation not well understood. We have previously shown, human prostate cancer, that transforming growth factor beta (TGFbeta)-mediated increases are dependent upon activation of the serine/threonine kinase, p38 MAP kinase. In current study, downstream effectors kinase were sought by first screening for proteins phosphorylated after TGFbeta treatment, only absence chemical inhibitors This led us to investigate mitogen-activated protein kinase-activated 2 (MAPKAPK2), known substrate as heat-shock 27 (HSP27), MAPKAPK2, both PC3 and PC3-M cells. After transient transfection, wild-type MAPKAPK2 HSP27 increased TGFbeta-mediated matrix metalloproteinase type (MMP-2) activity, invasion, which turn was inhibited SB203580, an inhibitor Conversely, dominant-negative blocked phosphorylation HSP27, whereas or mutant, non-phosphorylateable, each MMP-2, invasion. Similarly, knock down together, siRNA, also study demonstrates MMP-2 cancer.