期刊
ONCOTARGETS AND THERAPY
卷 8, 期 -, 页码 81-90出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/OTT.S70886
关键词
apoptosis; pituitary adenoma; APAF-1; cathepsin B; Ki-67; p53
资金
- POS-CCE, Romania [685-152/2010]
- Sectorial Operational Programme Human Resources Development (SOPHRD) - European Social Fund
- Romanian Government [POSDRU 141531]
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.
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