TIMP-1 regulation of cell cycle in human breast epithelial cells via stabilization of p27KIP1 protein

摘要: Increasing evidence suggests that tissue inhibitor of metalloproteinases-1 (TIMP-1) can directly regulate cell growth and apoptosis independent its matrix metalloproteinases (MMPs)-inhibitory activity. While TIMP-1's antiapoptotic activity has been well demonstrated, conflicting data reported regarding role in regulation. Here we show TIMP-1 reduces the rate human breast epithelial (MCF10A) cells by inducing cycle arrest at G(1). TIMP-1-mediated is associated with downregulation cyclin D(1) upregulation p27(KIP1), resulting inhibition cyclin-dependent kinase necessary for phosphorylation tumor suppressor retinoblastoma protein. We further modulation p27(KIP1) achieved through differential regulation protein stability factor signaling. also adhesion Whereas approximately 50% MCF10A reduced expression underwent death following loss (anoikis), overexpressing remained viable prominent without detectable death. Taken together, propose survival accompanied cells, although may not be a prerequisite general.