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Open Access Highly Accessed Research article

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

Kyou-Hoon Han1, Si-Hyung Lee1, Seon-Ah Ha2, Hyun Kee Kim2, CheWook Lee1, Do-Hyoung Kim1, Kee Hwan Gong2, JinAh Yoo2, Sanghee Kim2 and Jin Woo Kim23*

Author Affiliations

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

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

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

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BMC Cancer 2012, 12:274  doi:10.1186/1471-2407-12-274

Published: 2 July 2012

Abstract

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.

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