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 language | English (US) |
|---|---|
| Pages (from-to) | 6225-6232 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2006 |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells. / Song, Li Bing; Zeng, Mu Sheng; Liao, Wen Ting; Zhang, Ling; Mo, Hao Yuan; Liu, Wan Li; Shao, Jian Yong; Wu, Qiu Liang; Li, Man Zhi; Xia, Yun Fei; Fu, Li Wu; Huang, Wen Lin; Dimri, Goberdhan P.; Band, Vimla; Zeng, Yi Xin.
In: Cancer Research, Vol. 66, No. 12, 15.06.2006, p. 6225-6232.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells
AU - Song, Li Bing
AU - Zeng, Mu Sheng
AU - Liao, Wen Ting
AU - Zhang, Ling
AU - Mo, Hao Yuan
AU - Liu, Wan Li
AU - Shao, Jian Yong
AU - Wu, Qiu Liang
AU - Li, Man Zhi
AU - Xia, Yun Fei
AU - Fu, Li Wu
AU - Huang, Wen Lin
AU - Dimri, Goberdhan P.
AU - Band, Vimla
AU - Zeng, Yi Xin
PY - 2006/6/15
Y1 - 2006/6/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33745685884&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745685884&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-06-0094
DO - 10.1158/0008-5472.CAN-06-0094
M3 - Article
C2 - 16778197
AN - SCOPUS:33745685884
VL - 66
SP - 6225
EP - 6232
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 12
ER -