J Lung Cancer.  2006 Dec;5(2):111-113. 10.6058/jlc.2006.5.2.111.

Pro-apoptotic Cytochrome c Gene Mutation is Rare in Non-small Cell Lung Cancers

• Soung YH
• Lee SH

• KMID: 2200171
• DOI: http://doi.org/10.6058/jlc.2006.5.2.111

Abstract

PURPOSE: Several lines of evidence have indicated that the deregulation of apoptosis is involved in the mechanisms of cancer development, and somatic mutations of the apoptosis-related genes have been reported in human cancers. In addition to its role in oxidative phosphorylation, release of cytochrome c from the mitochondrial intermembrane space results in nuclear apoptosis. The aim of this study was to explore whether alteration of cytochrome c gene mutation is a characteristic of human non-small cell lung cancers (NSCLC).
MATERIALS AND METHODS
In the current study, to detect the somatic mutations in the DNA sequences encoding cytochrome c in 48 NSCLCs, we used polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and DNA sequencing.
RESULTS
The SSCP analysis revealed no mutation in the entire coding regions and all splice sites of human cytochrome c gene in the 48 NSCLCs.
CONCLUSION
The data presented here indicate that the pro-apoptotic cytochrome c may not be somatically mutated in human NSCLCs, and suggest that NSCLCs may not utilize mutational events of cytochrome c gene in the mechanisms for evading apoptosis.

Keyword

Non-small cell lung cancer; Cytochrome c; Apoptosis; Mutation

MeSH Terms

Apoptosis
Base Sequence
Carcinoma, Non-Small-Cell Lung
Clinical Coding
Cytochromes c*
Cytochromes*
Humans
Lung Neoplasms*
Lung*
Oxidative Phosphorylation
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Sequence Analysis, DNA
Cytochromes
Cytochromes c

Figure

• 

  Fig. 1. Representative SSCP of cytochrome c gene in the non-small cell lung cancers. The exon 2 of the cytochrome c gene was amplified by PCR using a specific primer set. The PCR products from the representative cases of non-small cell lung cancers were visualized on SSCP. SSCP of DNA from the non-small cell lung cancers (T) shows no aberrant bands as compared to SSCPs from the normal tissues (N).

Reference

1.Reed JC. Mechanisms of apoptosis. Am J Pathol. 2000. 39:1415–1430.

2.Nagata S. Apoptosis by death factor. Cell. 1997. 88:355–365.

3.Hanahan D., Weinberg RA. The hallmarks of cancer. Cell. 2000. 100:57–70.

4.Liu X: Kim CN: Yang J: Jemmerson R., Wang X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell. 1996. 86:147–157.

5.Soung YH., Lee JW., Kim HS, et al. Somatic mutations of CASP3 gene in human cancers. Hum Genet. 2004. 115:112–115.

6.Lee SH: Shin MS., Park WS, et al. Alterations of Fas (Apo-l/CD95) gene in non-small cell lung cancer. Oncogene. 1999. 18:3754–3760.

7.Lee SH: Shin MS., Kim HS, et al. Alterations of the DR5/TRAIL receptor 2 gene in non-small cell lung cancers. Cancer Res. 1999. 59:5683–5686.

8.Shin MS., Kim HS., Lee SH, et al. Alterations of Fas-pathway genes associated with nodal metastasis in non-small cell lung cancer. Oncogene. 2002. 21:4129–4136.

9.Lee JW., Soung YH., Nam SW., Lee JY., Yoo NJ: Lee SH. Mutational analysis of pro-apoptotic BAD gene in non-small cell lung cancer. J Lung Cancer. 2006. 5:35–38.

10.Soung YH., Lee UW., Moon SW, et al. Mutational analysis of caspase-7 and 8 genes in non-small cell lung cancer. J Lung Cancer. 2005. 4:38–41.

11.Soung YH., Lee JW., Kim SY, et al. Mutational analysis of pro-apoptotic caspase-9 gene in common human carcinomas. APMIS. 2006. 114:292–297.

12.Reed JC. Apoptosis-targeted therapies for cancer. Cancer Cell. 2003. 3:17–21.