Possible Relevance between Prohormone Convertase 2 Expression and Tumor Growth in Human Adrenocorticotropin-Producing Pituitary Adenoma

Abstract

Our study suggests that PC2 expression and Akt phosphorylation are related at the molecular level, resulting in a change in cell cycle and an increase in pituitary adenoma size. An elevation of plasma alphaMSH could conjecture the activation of the phosphatidylinositol 3/Akt cascade in PC2-positive APPAs and may become a valuable clinical marker of tumor growth in Cushing's disease.

Expression and clinical relevance of paired box protein 7 and sex determining region Y-box 2 in canine corticotroph pituitary adenomas

“…Although almost half of the human corticotroph adenomas in another study were positive for PC2 with immunohistochemistry (Iino et al, 2010), we were not able to identify PC2 positive cells in the canine pituitary samples, whereas the control tissue (canine testis) stained positive, suggesting a different expression pattern in canine pituitary tissue compared to human corticotroph adenomas. This altogether indicates that Pax7 and its downstream targets may play a species-dependent differential role in pituitary tumorigenesis.…”

“…The prohormone POMC is processed into ACTH in both melanotroph cells and corticotroph cells, followed by further cleavage into α-melanocyte stimulating hormone (α-MSH) by PC2 in melanotroph cells (Miller et al, 2003). In human corticotroph adenomas, 47% stained positive for PC2, whereas healthy pituitaries did not (Iino et al, 2010). Drd2 is expressed in melanotroph cells and inhibits α-MSH secretion (Garcia-Tornadu et al, 2010).…”

Treatment of Cushing's disease: a mechanistic update

“…Compared with corticotrope pituitary tumors that were histologically classified as pure adenomas, tumors identified as adenomatous hyperplasia or hyperplasia of ACTH-producing cells have higher PC2 expression and, although not statistically significant, higher neurofilament (NF) protein expression. Together, these results led to the hypothesis that CD may originate not only from corticotrope adenomas of the anterior lobe, but also from an adenoma or adenomatous hyperplasia of ACTH-producing cells of the intermediate zone because the PC2 enzyme is predominantly expressed in this region of the pituitary gland (Iino et al 2010). In addition, increases in the levels of alpha-melanocyte-stimulating hormone, which is a PC2 processing product, in the inferior petrosal sinus were higher in these patients.…”

“…In the pituitary gland, pro-opiomelanocortin (POMC) is cleaved by prohormone convertases (PCs) 1 and 2 (Bertagna 1994). PC1 (PCSK1) is expressed in both the anterior and intermediate pituitary lobes, whereas PC2 (PCSK2) expression is restricted to the intermediate lobe, which is believed to regress soon after birth and, therefore, is absent in adults (Bertagna 1994, Iino et al 2010). Lamberts and colleagues showed that D2 receptor agonist-responsive tumors located in the region consisted of basophilic adenomatous tissue or multiple microadenomas accompanied by hyperplastic cell nests (Lamberts et al 1980(Lamberts et al , 1982.…”

“…Lamberts and colleagues showed that D2 receptor agonist-responsive tumors located in the region consisted of basophilic adenomatous tissue or multiple microadenomas accompanied by hyperplastic cell nests (Lamberts et al 1980(Lamberts et al , 1982. PC2 expression at the intermediate lobe, and the phosphorylation of its cellsignaling molecule Akt, have been identified as clinical markers of an increased rate of tumor growth in CD (Iino et al 2010). Compared with corticotrope pituitary tumors that were histologically classified as pure adenomas, tumors identified as adenomatous hyperplasia or hyperplasia of ACTH-producing cells have higher PC2 expression and, although not statistically significant, higher neurofilament (NF) protein expression.…”