Pituitary Tumor Cells: Role of PKCα, PKCδ and PKCε Expression

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 speci fi c 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 PKC a and PKC e are usually involved in tumorigenesis and are the most expressed in human pituitary adenomas. The speci fi c PKC a and PKC e activation is closely associated with the tumoral pituitary cell proliferation and cell cycle progression through the ERK 1/2 pathway. By contrast, PKC d has been shown to mediate anti-proliferative and apoptotic signals. In the regression of pituitary tumors triggered by bromocriptine the PKC d /p38 pathway is involved in a non- apoptotic mechanism identi fi ed 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 speci fi c 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.