RESUMO
Cathepsins L and B are lysosomal cysteine proteinases whose activities and cellular location are altered in many types of cancers and cancer cell lines. Cathepsins L and B play an unspecified role in cancer invasion and metastasis. The purpose of our study was to determine whether cathepsins L and B are important for the ability of two prostate cancer cell lines, PC3 and DU 145, to invade the basement membrane-like preparation, Matrigel. Exposure of PC3 and DU145 to the irreversible cysteine proteinase inhibitor, E64, decreases the invasive ability of DU145, but not PC3. PC3 and DU145 were treated with the phorbol ester analogue, phorbol 12-myristate 13-acetate (PMA), a known tumor promoter that activates protein kinase C and contributes to the metastatic phenotype. PMA increased secreted cathepsin L+B activity and the invasive ability of PC3 and DU145; co-exposure to E64 and PMA decreased both cathepsin L+B activity and invasion. We conclude that DU145 requires cathepsin L+B activity more than PC3 for the invasion of the Matrigel. When the amount of secreted cathepsin L+B activity is increased by PMA treatment, however, PC3 becomes dependent on cathepsin L+B for invasion. Our study demonstrates that modulation of the amount of secreted cathepsin L+B activity influences the invasive phenotype of PC3 and DU145.
Assuntos
Catepsina B/metabolismo , Catepsinas/metabolismo , Colágeno , Cisteína Endopeptidases/metabolismo , Combinação de Medicamentos , Laminina , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteoglicanas , Catepsina B/efeitos dos fármacos , Catepsina L , Catepsinas/efeitos dos fármacos , Contagem de Células/métodos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cisteína Endopeptidases/efeitos dos fármacos , Humanos , Masculino , Estadiamento de Neoplasias/métodos , Acetato de TetradecanoilforbolRESUMO
The acquisition of automatic processing in persons with and without mental retardation was examined. In Experiment 1, subjects viewed slides of objects to determine whether a pictured object belonged to a designated target category. There was an effect of search set size for both groups that decreased and eventually disappeared with practice. This result reflected the acquisition of automatic processing. Also, evidence of automaticity was observed with less practice for subjects without relative to subjects with mental retardation. In Experiment 2, subjects searched for the presence of a designated target shape in arrays containing two, three, or four shapes. Results were essentially the same. Implications of these results for the development of cognitive skills by persons with mental retardation were discussed.