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- Title
Inactivating mutations of the Siah-1 gene in gastric cancer.
- Authors
Chang Jae Kim; Yong Gu Cho; Cho Hyun Park; Seong Whan Jeong; Suk Woo Nam; Su Young Kim; Sug Hyung Lee; Nam Jin Yoo; Jung Young Lee; Won Sang Park
- Abstract
SIAH-1: is the mammalian homolog of Drosophila seven in absentia (sina) and has been identified as a p53-inducible gene. Siah-1 can induce cell cycle arrests, tumor suppression, and apoptosis through a novelß-catenin degradation pathway. To determine whether genetic alterations of Siah-1 gene are involved in the development and/or progression of gastric cancer, we searched for mutation of the Siah-1 gene in 95 gastric cancers by single-strand conformational polymorphism and sequencing. The effect of Siah-1 onß-catenin degradation was further examined in wild- and mutant-type Siah-1-transfected HEK 293T cells. We found two missense mutations of the Siah-1 gene. The cases with Siah-1 mutation showed nuclear translocation and cytoplasmic staining ofß-catenin. Interestingly, two mutants of Siah-1 stabilized cytoplasmic levels ofß-catenin, even after treatment of adriamycin. Furthermore, both mutants failed to suppress cyclin D1 expression and to induce apoptosis. These data suggest that inactivating mutations of the Siah-1 may contribute to the development of gastric cancer throughß-catenin stabilization and apoptosis block.Oncogene (2004) 23, 8591-8596. doi:10.1038/sj.onc.1208113 Published online 4 October 2004
- Subjects
GENETIC polymorphisms; DROSOPHILA; CELL death; APOPTOSIS; DOXORUBICIN; CELLS
- Publication
Oncogene, 2004, Vol 23, Issue 53, p8591
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208113