The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis

BMC Cancer

Jin Woo Kim²  Sanghee Kim³  JinAh Yoo³  Kee Hwan Gong³  Do-Hyoung Kim¹  CheWook Lee¹  Hyun Kee Kim³  Seon-Ah Ha³  Si-Hyung Lee¹  Kyou-Hoon Han¹ 

[1]Division of Biosystems Research, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, South Korea

[2]Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

[3]Molecular Genetic Laboratory, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

关键词: Anti-cancer agents;    Three-dimensional structure;    GIG47;    Oncogene;    Breast cancer;   

Others  :  1080333
DOI  :  10.1186/1471-2407-12-274

 received in 2011-12-25, accepted in 2012-07-02,  发布年份 2012

【 摘 要 】

Background

A candidate oncogene GIG47, previously known as a neudesin with a neurotrophic activity, was identified by applying the differential expression analysis method.

Methods

As a first step to understand the molecular role of GIG47, we analyzed the expression profile of GIG47 in multiple human cancers including the breast cancer and characterized its function related to human carcinogenesis. Based on this oncogenic role of GIG47, we then embarked on determining the high-resolution structure of GIG47. We have applied multidimensional heteronuclear NMR methods to GIG47.

Results

GIG47 was over-expressed in primary breast tumors as well as other human tumors including carcinomas of the uterine cervix, malignant lymphoma, colon, lung, skin, and leukemia. To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 cells. The ectopic expression of GIG47 in MCF7 cells promoted the invasiveness in the presence of 50% serum. In addition, it also resulted in the increased tumorigenicity in in vivo tumor formation assay. The tumorigenesis mechanism involving GIG47 might be mediated by the activation of MAPK and PI3K pathways. These results indicate that GIG47 plays a role in the breast tumorigenesis, thus representing a novel target for the treatment of breast cancer. To facilitate the development of GIG47-targeted therapeutics, we determined the structural configuration of GIG47. The high-resolution structure of GIG47 was obtained by combination of NMR and homology modeling. The overall structure of GIG47 has four α-helices and 6 β-strands, arranged in a β1-α1-β2-β3-α2-β4-α3-α4-β5-β6 topology. There is a potential heme/steroid binding pocket formed between two helices α2 and α3.

Conclusion

The determined three-dimensional structure of GIG47 may facilitate the development of potential anti-cancer agents.

【 授权许可】

   
2012 Han et al.; licensee BioMed Central Ltd.

【 图 表 】

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