Protein kinase C activity and expression in normal and adenomatous human pituitaries

Abstract

Protein kinase C (PKC) activity and expression were measured in 54 adenomas (prolactin (PRL)-, growth hormone (GH)- and non-secreting), 1 of them obtained from a patient treated with the dopamine agonist bromocriptine and 2 from patients treated with the somatostatin analog octreotide. They were also measured in normal human and rat pituitaries. Total PKC activity was measured by incorporation of 32P into histones, and PKC expression by dot blot immunoquantification using purified PKC as a standard. Both enzyme activity and expression were higher in adenomatous pituitaries than in normal human or rat pituitaries. PKC expression in GH-secreting and non-secreting tumors was significantly higher than that in PRL-secreting tumors. Furthermore, it was significantly higher invasive tumors than in non-invasive tumors. In the 3 adenomas which were obtained from patients treated with bromocriptine or octreotide and which were used for PKC-activity measurement, particulate- and soluble-PKC activities were significantly lower than those measured in non-treated adenomas.

Ectopic expression of a mutant form of PKCα originally found in human tumors: aberrant subcellular translocation and effects on growth control

“…32 were selected for analysis. They expressed around 20 times the protein (624 and 619 respectively), which is consistent with the maximum increase in PKCa expression found in pituitary tumors (Alvaro et al, 1992(Alvaro et al, , 1993. Two R6-hPKCa-wt clones were also selected for analysis, no.…”

Matrix Metalloproteinase-9 Is Differentially Expressed in Nonfunctioning Invasive and Noninvasive Pituitary Adenomas and Increases Invasion in Human Pituitary Adenoma Cell Line

“…PKC has been implicated in the invasion of a number of tumor cells, including astrocytomas, 44 urinary bladder carcinomas, 45 colon carcinomas, 46 and breast cancers. 47 Initial observation of a point mutation of PKC-␣ and a higher overall PKC activity and expression in invasive PAs reported by Alvaro and colleagues 4,5 was not confirmed by others. 6 However, a host of growth factors (including TGF-␣, epidermal growth factor) and their receptors are overexpressed in PA. 16,48,49 Activation of these G-protein coupled receptors may lead to the stimulation of phospholipase C (PLC) and subsequent generation of inositol triphosphate (IP3) and diacylglycerol, an activator of PKC.…”

“…3 A point mutation of protein kinase C (PKC)-␣ and a higher overall PKC activity and expression have been documented in invasive PAs. 4,5 However, other investigators have failed to detect such a change. 6 Reduced conventional PKC activity had been observed in some cases of prolactinomas that responded favorably to exogenous dopamine agonists, 7 and dose-dependent inhibition of cell growth in pituitary tumor cell culture by hypericin (a PKC inhibitor) also had been demonstrated.…”

Activation of protein kinase C promotes human cancer cell growth through downregulation of p18INK4c

“…Situated at the crossroads of many signal transduction pathways, PKCs are activated by upstream signaling elements such as growth factor receptors (for example, platelet-derived growth factor receptor), and are able to activate downstream signaling molecules such as the proto-oncogene Raf-1 (Schenk and Snaar-Jagalska, 1999;Liebmann, 2001). In fact, PKC activity is increased in some human tumors compared with their normal counterpart (O'Brian et al, 1989;Alvaro et al, 1992;Gordge et al, 1996). Furthermore, a large variety of structurally and mechanistically distinct PKC inhibitors were reported to have potent antitumor activity in vitro and in vivo (Goekjian and Jirousek, 2001;Swannie and Kaye, 2002;da Rocha et al, 2002).…”