Journal Article

Inactivating mutations of proapoptotic <i>Bad</i> gene in human colon cancers

Jong Woo Lee, Young Hwa Soung, Su Young Kim, Suk Woo Nam, Chang Jae Kim, Yong Gu Cho, Jong Heun Lee, Hong Sug Kim, Won Sang Park, Sang Ho Kim, Jung Young Lee, Nam Jin Yoo and Sug Hyung Lee

in Carcinogenesis

Volume 25, issue 8, pages 1371-1376
Published in print August 2004 | ISSN: 0143-3334
Published online August 2004 | e-ISSN: 1460-2180 | DOI:
Inactivating mutations of proapoptotic Bad gene in human colon cancers

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Evidence exists that deregulation of apoptosis is involved in the mechanisms of cancer development, and the somatic mutations of apoptosis-related genes have been reported in human cancers. Bcl-XL/Bcl-2-associated death promoter (Bad), a proapoptotic member of Bcl-2 family, plays an important role in the intrinsic apoptosis pathway. To explore the possibility that the genetic alterations of Bad might be involved in the development of human cancers, we analyzed the entire coding region and all splice sites of human Bad gene in 47 colon adenocarcinomas. Overall, we detected two somatic missense mutations (4.3%) in Bad gene. Interestingly, both of the Bad mutations were detected in the gene sequences encoding the Bcl-2 homology3 domain of Bad, which has a crucial role in inducing cell death. Transfection study revealed that both of the tumor-derived Bad mutants had decreased apoptosis activities compared with the wild-type Bad, indicating that the Bad mutations reduced the cell death function of Bad. Co-immunoprecipitation assay revealed that binding of one of the tumor-derived Bad mutants with Bcl-2 and Bcl-XL is reduced. This is the first report on Bad gene mutation in human malignancies, and our data suggest that Bad gene is occasionally mutated in colon cancers and that somatic mutation of Bad may contribute to the development of colon cancers.

Keywords: Bad, Bcl-XL/Bcl-2-associated death promoter; BH, Bcl-2 homology; BH3, Bcl-2 homology3; PCR, polymerase chain reaction; SSCP, single strand conformation polymorphism

Journal Article.  3765 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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