대장암에서 세포자멸사 유발성 bcl-2 Family 유전자의 돌연변이 연구
Mutational Analysis of Proapoptotic bcl-2 Family genes in Colon Carcinomas
2
조회
0
다운로드
5
인용
0
참고문헌
초록
Abstract
Background : Several lines of evidence have indicated that the deregulation of apoptosis is involved in the mechanisms of cancer development, and somatic mutations of the apoptosisrelated genes have been reported in human cancers. Members of the bcl-2 family proteins regulate the intrinsic apoptosis pathway mainly in the mitochondria. The aim of this study was to explore whether the somatic mutation of the proapoptotic bcl-2 family genes, one of the mechanisms that prolong the survival of cancer cells, occurred in colorectal carcinomas. Methods : In the current study, to detect the somatic mutations in the DNA sequences encoding the bcl-2 homology 3 (BH3) domain of the human bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G, and bmf genes in 98 colon adenocarcinomas, we used polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing. Results : The SSCP analysis detected no evidence of somatic mutations of the genes in the coding regions of the BH3 domain in the cancers. Conclusions : The data presented here indicate that the proapoptotic bcl-2 family genes, bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G and bmf may not be somatically mutated in human colorectal carcinomas, and suggest that the colorectal cancers may not utilize mutational events of these proapoptotic bcl-2 family genes in the mechanisms for evading apoptosis.
참고문헌 (22)
- "Mechanisms of apoptosis", 157, pp.1415~30 (2000)
- "Apoptosis by death factor", 88, pp.355~65 (1997)
- "The hallmarks of cancer", 100, pp.57~70 (2000)
- "14-3-3 proteins and survival kinasescooperate to inactivate BAD by BH3 domain phosphorylation", 6, pp.41~51 (2000)
- "Bim:a novel member ofthe Bcl-2 family that promotes apoptosis", 17, pp.384~95 (1998)
- "encodes a protein that activates apoptosis and interactsselectively with survival-promoting proteins Bcl-2 and Bcl-X", 16(hara n), pp.1686~94
- "Bcl-G,a novel pro-apoptotic member ofthe Bcl-2 family", 276, pp.2780~5 (2001)
- "Noxa,a BH3-only member of theBcl-2 family and candidate mediator of p53-induced apoptosis", 288, pp.1053~8 (2000)
- "PUMA,a novel proapoptotic gene,is in-duced by p53", 7, pp.683~94 (2001)
- "Survival of patients with metastatic breast carcinoma:importance ofprognostic markers of the primary tumor", 97, pp.545~53 (2003)
- "Expression ofBcl-2 family member Bid in normal and malignant tissues", 4, pp.129~40 (2002)
- "bcl-2-immunoglobulin trans-genic mice demonstrate extended B cell survival and follicular lym-phoproliferation", 57, pp.79~88 (1989)
- "Inactivating mutation of the pro-apoptotic gene BID in gastric cancer", 202, pp.439~45 (2004)
- "Mutations of the bak genein human gastric and colorectal cancers", 60, pp.4328~30 (2000)
- "Somatic frameshift muta-tions in the BAX gene in colon cancers of the microsatellite mutatorphenotype", 275, pp.967~9 (1997)
- "Inactivating mutations of proapopto-tic Bad gene in human colon cancers", 25, pp.1371~6
- "A simple,pre-cise,and economical microdissection technique for analysis of genomicDNA from archival tissue sections", 433, pp.305~9 (1998)
- "Alterations of Fas(Apo-1", CD95)gene in non-small cell lung cancer, 1999, pp.18, 3754~60
- "Mutations of tumor necrosis factorrelated apoptosis-inducing ligand receptor 1 genes in metastatic breast cancers", 61, pp.4942~6
- "Inactivating mutations of CASP10 gene in non-Hodgkin lymphomas", 99, pp.4094~9 (2002)
- "Prognostic value of bcl-2 oncoprotein expression in stage II colon carcinoma", 1, pp.1103~10 (1995), Clin Cancer Res
- "Apoptosis-targeted therapies for cancer", 3, pp.17~22 (2003)