RESUMO

Intracellular progesterone receptors (PRs) and protein kinases C (PKCs) are known regulators of cancer cell proliferation and metastasis. Both PRs and PKCs are found overexpressed in grade IV human astrocytomas, also known as glioblastomas, which are the most frequent and aggressive brain tumors. In the present study, we investigated whether PR activation by PKC induces the migration and invasion of glioblastoma derived cell lines and if PKCα and δ isoforms are involved in PR activation. We observed that PKC activation with tetradecanoylphorbol acetate (TPA) increases the migration and invasion capacity of two human glioblastoma derived human cell lines (U251 MG and U87) and that the treatment with the PR receptor antagonist RU486 blocks these processes. Interestingly, the pharmacological inhibition of the isoenzymes PKCα and PKCδ also resulted in a blocked PR transcriptional activity. Also, TPA-dependent PR activation increases the expression of progesterone-induced blocking factor (PIBF), a known PR target gene. These results hint to an existing cross-talk between PKCs and PRs in regulating the infiltration process of human glioblastomas.

Assuntos

Regulação Neoplásica da Expressão Gênica , Neuroglia/metabolismo , Proteína Quinase C-alfa/genética , Proteína Quinase C-delta/genética , Receptores de Progesterona/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antagonistas de Hormônios/farmacologia , Humanos , Mifepristona/farmacologia , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Proteínas da Gravidez/genética , Proteínas da Gravidez/metabolismo , Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-delta/metabolismo , Receptores de Progesterona/antagonistas & inibidores , Receptores de Progesterona/metabolismo , Transdução de Sinais , Fatores Supressores Imunológicos/genética , Fatores Supressores Imunológicos/metabolismo , Acetato de Tetradecanoilforbol/farmacologia