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

Je Sang Ko, Young Han Lee, Seung Yong Hwang, Youn Soo Lee, Seung Min Shin, Jae Hoon Hwang, Jin Kim, Yong Wook Kim, Sung Wuk Jang, Zae Young Ryoo, In Kyung Kim, Sung Eun Namkoong, Jin Woo Kim

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50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4679-4689
Number of pages11
JournalOncogene
Volume22
Issue number30
DOIs
Publication statusPublished - 2003 Jul 24
Externally publishedYes

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Keywords

  • Cervical cancer
  • HCCR-2
  • Oncogene
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Ko, J. S., Lee, Y. H., Hwang, S. Y., Lee, Y. S., Shin, S. M., Hwang, J. H., Kim, J., Kim, Y. W., Jang, S. W., Ryoo, Z. Y., Kim, I. K., Namkoong, S. E., & Kim, J. W. (2003). Identification and differential expression of novel human cervical cancer oncogene HCCR-2 in human cancers and its involvement in p53 stabilization. Oncogene, 22(30), 4679-4689. https://doi.org/10.1038/sj.onc.1206624