DN-R175H p53 mutation is more effective than p53 interference in inducing epithelial disorganization and activation of proliferation signals in human carcinoma cells: role of E-cadherin.

摘要: One of the hallmarks carcinomas is epithelial disorganization, linked to overexpression matrix metalloproteases (MMP) like MMP-9, loss intercellular E-cadherin and activation epidermal growth receptor (EGFR/erbB1). Since p53 tumor suppressor pathway inactivated in most human cancers due gene mutations or defective wt signaling, we now investigated breast carcinoma MCF-7 cells, whether single treatment with transactivation pharmacological inhibitor pifithrin-α, transient siRNA interference stable insertion a dominant-negative (DN) R175H mutant increase: (i) EGFR/erbB1 activation, (ii) MMP-9 expression (iii) surface E-cadherin. Transient abrogation function increased phosphorylation expression. However, all these effects were much more pronounced cells stably transduced dominant negative–Arg-175His (DN-R175H p53), which also showed cytoarchitecture extensive downregulation. Collectively, results support notion that DN-R175H exerts gain oncogenic by promoting disruption contacts proliferation signals. Our data suggests shape control are unequally affected depending on how impaired partial full activity lost. © 2009 UICC