Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells

Li Bing Song, Mu Sheng Zeng, Wen Ting Liao, Ling Zhang, Hao Yuan Mo, Wan Li Liu, Jian Yong Shao, Qiu Liang Wu, Man Zhi Li, Yun Fei Xia, Li Wu Fu, Wen Lin Huang, Goberdhan P. Dimri, Vimla Band, Yi Xin Zeng

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292 Scopus citations

Abstract

The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be overexpressed in 29 of 75 nasopharyngeal carcinoma tumors (38.7%) by immunohistochemical analysis. In contrast to nasopharyngeal carcinoma, there was no detectable expression of Bmi-1 in noncancerous nasopharyngeal epithelium. Moreover, high Bmi-1 expression positively correlated with poor prognosis of nasopharyngeal carcinoma patients. We also report that the overexpression of Bmi-1 leads to bypass of senescence and immortalization of NPECs, which normally express p16INK4a and exhibit finite replicative life span. Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16 INK4a expression. Mutational analysis of Bmi-1 showed that both RING finger and helix-turn-helix domains of it are required for immortalization of NPECs. Our findings suggest that Bmi-1 plays an important role in the development and progression of nasopharyngeal carcinoma, and that Bmi-1 is a valuable marker for assessing the prognosis of nasopharyngeal carcinoma patients. Furthermore, this study provides the first cellular proto-oncogene immortalized nasopharyngeal epithelial cell line, which may serve as a cell model system for studying the mechanisms involved in the tumorigenesis of nasopharyngeal carcinoma.

Original languageEnglish (US)
Pages (from-to)6225-6232
Number of pages8
JournalCancer Research
Volume66
Issue number12
DOIs
StatePublished - Jun 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Song, L. B., Zeng, M. S., Liao, W. T., Zhang, L., Mo, H. Y., Liu, W. L., Shao, J. Y., Wu, Q. L., Li, M. Z., Xia, Y. F., Fu, L. W., Huang, W. L., Dimri, G. P., Band, V., & Zeng, Y. X. (2006). Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. Cancer Research, 66(12), 6225-6232. https://doi.org/10.1158/0008-5472.CAN-06-0094