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Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization

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Abstract

Basic studies of oncogenesis have demonstrated that either the elevated production of particular oncogene proteins or the occurrence of qualitative abnormalities in oncogenes can contribute to neoplastic cellular transformation. The purpose of this study was to identify unique oncogenes that are differentially expressed in human cancers and characterize their functions in tumorigenesis. To discover new putative oncogenes, the differential display RT–PCR method was applied using normal cervical tissues, cervical cancer cell lines, cervical cancer tissues, and metastatic tissues. We identified a new human cervical cancer oncogene HCCR-2 that was overexpressed in various human tumors including leukemia, lymphoma, and carcinomas of the breast, kidney, ovary, stomach, colon, and uterine cervix. Ectopic expression of HCCR-2 resulted in direct tumorigenic conversions of NIH/3T3 and Rat1 fibroblasts. Nude mice injected with NIH/3T3 cells stably transfected with HCCR-2 formed tumors in 4 weeks. The resultant tumors display characteristics of an epithelial carcinoma. In HCCR-2 transfected NCI-H460 cells and RKO cells, stabilization of the p53 tumor suppressor occurred without genetic mutation and correlated with functional impairment, as indicated by the defective induction of p53-induced p21WAF1, MDM2, and bax. These results indicate that HCCR-2 probably represents a new oncogene that is related to tumorigenesis, functioning as a negative regulator of the p53 tumor suppressor.

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Acknowledgements

Supported by a Grant (HMP-99-B-02-0002) of the 1999, Good Health R&D Project, Ministry of Health & Welfare, ROK. We thank JY Jung and W Kim for critically reading the manuscript.

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Authors and Affiliations

  1. Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, 138-736, South Korea

    Jesang Ko & Sung-Wuk Jang

  2. Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu, 705-717, South Korea

    Young Han Lee

  3. Department of Biochemistry and Molecular Biology, Hanyang University, Ansan, 425-791, South Korea

    Seung Yong Hwang & Jae Hoon Hwang

  4. Department of Clinical Pathology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

    Youn Soo Lee

  5. Molecular Genetic Laboratory and Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

    Seung Min Shin, Yong Wook Kim, In-Kyung Kim, Sung Eun Namkoong & Jin Woo Kim

  6. Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

    Jin Kim

  7. Laboratory of Animal Science, College of Medicine, The Catholic University of Korea, Seoul, 137-040, South Korea

    Zae Young Ryoo

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  1. Jesang Ko
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  2. Young Han Lee
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  7. Jin Kim
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  13. Jin Woo Kim
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Correspondence to Jin Woo Kim.

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Ko, J., Lee, Y., Hwang, S. et al. Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization. Oncogene 22, 4679–4689 (2003). https://doi.org/10.1038/sj.onc.1206624

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