title: Decreased expression of APAF-1 and increased expression of cathepsin B in invasive pituitary adenoma.
abstract: OBJECTIVE
  Apoptotic protease-activating factor-1 (APAF-1) and cathepsin B are important functional proteins in apoptosis; the former is involved in the intrinsic (mitochondrial) pathway, while the latter is associated with both intrinsic and extrinsic pathways. Changes in the expression of apoptosome-related proteins could be useful indicators of tumor development since a priori defects in the mitochondrial pathway might facilitate the inception and progression of human neoplasms. Our aim was to evaluate the profiles of APAF-1 and cathepsin B in relation with other molecules involved in apoptosis/proliferation and to correlate them with the aggressive behavior of invasive pituitary adenomas.
  
  
  METHODS
  APAF-1 and cathepsin B were assessed in tissue samples from 30 patients with pituitary adenomas, of which 16 were functional adenomas and 22 were invasive adenomas.
  
  
  RESULTS
  A positive relationship between high proliferation and invasiveness was observed in invasive pituitary adenomas when compared to their noninvasive counterparts (Ki-67 labeling index - 4.72% versus 1.75%). Decreased expression of APAF-1 was recorded in most of the invasive adenomas with a high proliferation index, while the cathepsin B level was elevated in this group. We have noticed a negative correlation between the low level of APAF-1 and invasiveness (63.63%; P<0.01); at the same time, a positive correlation between cathepsin B expression and invasiveness (59.09%; P<0.01) was found. In all, 81.25% out of the total APAF-1-positive samples were cathepsin B negative (P<0.01); 76.92% out of the total cathepsin B-positive samples were APAF-1-negative (P<0.01). These results were reinforced by an apoptosis protein array examination, which showed inhibition of the extrinsic apoptotic pathway in an invasive pituitary adenoma.
  
  
  CONCLUSIONS
  A bidirectional-inverted relationship between APAF-1 and cathepsin B expressions was noticed. One might hypothesize that shifting the balance between mediators of cell death could result in changes in tumor behavior.
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Tanase
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania ; National Institute for Chemical Pharmaceutical R&D, Department of Biochemistry, Bucharest, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Albulescu
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania.
authors.forename: Elena
authors.initials: E
authors.lastname: Codrici
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy, Department of Biochemistry, Bucharest, Romania.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Calenic
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania.
authors.forename: Ionela Daniela
authors.initials: ID
authors.lastname: Popescu
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania.
authors.forename: Simona
authors.initials: S
authors.lastname: Mihai
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania ; Stefan S. Nicolau Institute of Virology, Cellular and Molecular Pathology, Cellular and Molecular Medicine Department, Bucharest, Romania.
authors.forename: Laura
authors.initials: L
authors.lastname: Necula
authors.affiliation: "Carol Davila" University of Medicine and Pharmacy, Cellular and Molecular Medicine Department, Bucharest, Romania.
authors.forename: Maria Linda
authors.initials: ML
authors.lastname: Cruceru
authors.affiliation: "Victor Babes" National Institute of Pathology, Biochemistry-Proteomics Department, Bucharest, Romania ; "Carol Davila" University of Medicine and Pharmacy, Cellular and Molecular Medicine Department, Bucharest, Romania.
authors.forename: Mihail Eugen
authors.initials: ME
authors.lastname: Hinescu
keywords: APAF-1; Ki-67; apoptosis; cathepsin B; p53; pituitary adenoma