Protein Kinase C δ Involvement in Mammary Tumor Cell Metastasis

摘要: Metastasis requires cytoskeletal remodeling for migration, adhesion, and extravasation of metastatic cells. Although protein kinase C (PKC) is involved in tumor promotion/progression remodeling, its role metastasis has not been defined. PKCδ levels are increased highly 13762NF mammary cells (MTLn3) compared with less metastatic, parental cell lines. To determine whether the increase endogenous functionally related to their potential, we prepared MTLn3 that express inhibitory regulatory domain fragment (RDδ) under control a tetracycline-inducible promoter. RDδ expression attenuated PKC activity, as demonstrated by decreased phosphorylation substrate adducin migrating Thus, MT cells, appears primarily influence cytoskeleton-dependent processes rather than cycle progression. influenced potential vivo, MTLn3/RDδ were either grown fat pad or injected into tail vein syngeneic rats, effects doxycycline-induced on pulmonary metastases studied. Consistent vitro data, induction significantly reduced number lung without affecting growth primary tumor. These results suggest interfering activity expressing inhibits cytoskeleton-regulated important metastasis.