TY - JOUR
T1 - Possible relevance between prohormone convertase 2 expression and tumor growth in human adrenocorticotropin-producing pituitary adenoma
AU - Iino, Kazumi
AU - Oki, Yutaka
AU - Yamashita, Miho
AU - Matsushita, Fumie
AU - Hayashi, Chiga
AU - Yogo, Kosuke
AU - Nishizawa, Shigeru
AU - Yamada, Shozo
AU - Maekawa, Masato
AU - Sasano, Hironobu
AU - Nakamura, Hirotoshi
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2010/8
Y1 - 2010/8
N2 - Context: Methods for preoperative diagnosis of prohormone convertase 2 (PC2)-positive ACTH-producing pituitary adenomas (APPAs) have not been established. Also, their characteristics are not evident. Objective: This study was designed to understand the meaning of plasma αMSH levels and the role of cell proliferation-signaling molecules in PC2-positive APPAs. Patients and Main Outcome Measures: Nineteen human APPAs (four males and 15 females) were examined for the expression of PC2, phosphorylated ERK1/2, phosphorylated Akt1/2/3 (p-Akt) and receptor tyrosine kinases. αMSH was measured in extracted plasma from 17 APPA patients and 30 healthy volunteers. Results: Nine adenomas (47.4%) were immunopositive for PC2 and were large and invasive in nature. In all normal controls and eight PC2-negative cases, plasma αMSH was undetectable, whereas in four PC2-positive cases, it was detected at abnormally higher levels. Eight adenomas (42.1%) were immunopositive for both PC2 and p-Akt, and seven others (36.8%) were immunonegative for both, suggesting significant coexpression of PC2 and p-Akt in tumors. Quantitative RT-PCR revealed that PC2 expression is associated with phosphorylation of Akt but not with its gene expression. Most APPAs expressed receptor tyrosine kinases, but membrane-bound receptors could not be identified. Conclusions: 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 αMSH 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.
AB - Context: Methods for preoperative diagnosis of prohormone convertase 2 (PC2)-positive ACTH-producing pituitary adenomas (APPAs) have not been established. Also, their characteristics are not evident. Objective: This study was designed to understand the meaning of plasma αMSH levels and the role of cell proliferation-signaling molecules in PC2-positive APPAs. Patients and Main Outcome Measures: Nineteen human APPAs (four males and 15 females) were examined for the expression of PC2, phosphorylated ERK1/2, phosphorylated Akt1/2/3 (p-Akt) and receptor tyrosine kinases. αMSH was measured in extracted plasma from 17 APPA patients and 30 healthy volunteers. Results: Nine adenomas (47.4%) were immunopositive for PC2 and were large and invasive in nature. In all normal controls and eight PC2-negative cases, plasma αMSH was undetectable, whereas in four PC2-positive cases, it was detected at abnormally higher levels. Eight adenomas (42.1%) were immunopositive for both PC2 and p-Akt, and seven others (36.8%) were immunonegative for both, suggesting significant coexpression of PC2 and p-Akt in tumors. Quantitative RT-PCR revealed that PC2 expression is associated with phosphorylation of Akt but not with its gene expression. Most APPAs expressed receptor tyrosine kinases, but membrane-bound receptors could not be identified. Conclusions: 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 αMSH 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.
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U2 - 10.1210/jc.2009-2716
DO - 10.1210/jc.2009-2716
M3 - Article
C2 - 20501680
AN - SCOPUS:77955407838
VL - 95
SP - 4003
EP - 4011
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -