Decreased expression of APAF-1 and increased expression of cathepsin B in invasive pituitary adenoma

Abstract

Purpose

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.

Materials and 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.

Conclusion

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.

Keywords:

• apoptosis
• pituitary adenoma
• APAF-1
• cathepsin B
• Ki-67
• p53

Acknowledgments

The research presented in this paper was supported by the grants POS-CCE 685–152/2010, Romania.

This paper is partly supported by the Sectorial Operational Programme Human Resources Development (SOPHRD), financed by the European Social Fund and the Romanian Government under the contract number POSDRU 141531.

The authors present special thanks to Dr Vasile Ciubotaru from the Neurology Department of Bagdasar-Arseni Hospital for providing the samples of patients’ tumors, and to Dr Dorel Arsene for providing the pathological diagnosis.

The authors would like to thank Irina Radu, certified translator in Medicine – Pharmacy, certificate credentials: series E number 0048, for professional linguistic assistance.

Disclosure

The authors report no conflicts of interest in this work.