Pituitary Tumor Cells: Role of PKCalfa, PKCepsilon and PKCdelta expression

PETITI JP; TORRES AI

TUMORS OF THE CENTRAL NERVOUS SYSTEM

Springer

Año: 2012;

ABSTRACT The PKC family is involved in a wide variety of cellular processes such as proliferation, senescence and cell death, which are determined by the specific subcellular targeting of these kinases. In adenomatous pituitary cells, it has been observed that the enzyme activity and expression of PKCs were higher than in normal pituitary. The isozymes PKCalfa and PKCepsilon are usually involved in tumorigenesis and are the most expressed in human pituitary adenomas. The specific PKCalfa and PKCepsilon activation is closely associated with the tumoral pituitary cell proliferation and cell cycle progression through the ERK 1/2 pathway. By contrast, PKCdelta has been shown to mediate anti-proliferative and apoptotic signals. In the regression of pituitary tumors triggered by bromocriptine the PKCdelta/p38 pathway is involved in a non-apoptotic mechanism identified as parapoptosis. Each individual PKC isozyme is undoubtedly an attractive target for therapeutic intervention, given its role in survival and cell death in pituitary tumors, processes that contribute to the onset and progression of the tumorigenesis. The combination of specific inhibitors of PKC and the ?upstream-downstream? kinases of the signalling pathways with conventional antitumoral drugs could lead to a better tolerance and effectiveness in the regression of pituitary tumors.