title: Possible relevance between prohormone convertase 2 expression and tumor growth in human adrenocorticotropin-producing pituitary adenoma.
abstract: BACKGROUND
  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 alphaMSH levels and the role of cell proliferation-signaling molecules in PC2-positive APPAs.
  
  
  METHODS
  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. alphaMSH 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 alphaMSH 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 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.
authors.affiliation: Second Division, Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Iino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oki
authors.forename: Miho
authors.initials: M
authors.lastname: Yamashita
authors.forename: Fumie
authors.initials: F
authors.lastname: Matsushita
authors.forename: Chiga
authors.initials: C
authors.lastname: Hayashi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Yogo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Nishizawa
authors.forename: Shozo
authors.initials: S
authors.lastname: Yamada
authors.forename: Masato
authors.initials: M
authors.lastname: Maekawa
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D049913:ACTH-Secreting Pituitary Adenoma / Q000235:genetics / Q000378:metabolism*; D000236:Adenoma / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D045706:Proprotein Convertase 2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000521:alpha-MSH / Q000097:blood*
chemical_list: D012333:RNA, Messenger; D000521:alpha-MSH; D048052:Mitogen-Activated Protein Kinase 3; D045706:Proprotein Convertase 2