Nuclear localization of apoptosis protease activating factor-1 predicts survival after tumor resection in early-stage non-small cell lung cancer.

Abstract

The proapoptotic protein apoptosis protein activating factor-1 (Apaf-1), which is normally located in the cytoplasm, can translocate to the nucleus before non-small cell lung carcinoma (NSCLC) cells manifest signs of apoptosis such as mitochondrial damage, caspase activation, or chromatin condensation. This may indicate a stage of imminent apoptosis. Importantly, we found that 24% (15 of 62) of resected stage I NSCLC (T(1)N(0)M(0) or T(2)N(0)M(0)), manifested a marked nuclear localization of Apaf-1 (Apaf-1(Nuc)), as compared with the mostly cytoplasmic localization of Apaf-1 found in the remaining tumors (Apaf-1(Cyt)). After a median follow-up of 6.31 years, the actuarial 5-year overall survival rates were 89% (56-98%) in the Apaf-1(Nuc) group and 54% (36-71%) in the Apaf-1(Cyt) group (P = 0.039). No correlation between the subcellular localization of Apaf-1 and that of p53 and Hsp70 could be established. Thus, the subcellular location of Apaf-1 (but not that of p53 or Hsp70) constitutes an accurate prognostic factor for overall survival in NSCLC.

• Authors: Benjamin Besse, Céline Candé, Jean-Philippe Spano, Antoine Martin, David Khayat, Thierry Le Chevalier, Thomas Tursz, Laure Sabatier, Jean-Charles Soria, Guido Kroemer
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 17 Pg. 5665-9 (Sep 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15355891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• APAF1 protein, human
• Apoptotic Protease-Activating Factor 1
• Chromatin
• Proteins
• Caspases

Topics

• Adult
• Aged
• Aged, 80 and over
• Apoptotic Protease-Activating Factor 1
• Carcinoma, Non-Small-Cell Lung (enzymology, mortality, surgery)
• Caspases (metabolism)
• Cell Nucleus (enzymology)
• Chromatin (metabolism)
• Cytoplasm (metabolism)
• Enzyme Activation
• Female
• Humans
• Lung Neoplasms (enzymology, mortality)
• Male
• Middle Aged
• Mitochondria (metabolism)
• Neoplasm Staging
• Predictive Value of Tests
• Protein Transport
• Proteins (metabolism)
• Subcellular Fractions
• Survival Rate