Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet litt...

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Main Authors: Li Xiangping, Weng Desheng, Wu Lirong, Li Gang, Wu Zhengrong, Yao Kaitai
Format: Article
Language:English
Published: BMC 2009-09-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/9/315
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author Li Xiangping
Weng Desheng
Wu Lirong
Li Gang
Wu Zhengrong
Yao Kaitai
author_facet Li Xiangping
Weng Desheng
Wu Lirong
Li Gang
Wu Zhengrong
Yao Kaitai
author_sort Li Xiangping
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines.</p> <p>Methods</p> <p>The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, <it>in vivo</it>, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument.</p> <p>Results</p> <p>The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17) cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37) cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (<it>p </it>= 0.034), distant metastasis (<it>p </it>= 0.036), and clinical stage (<it>p = </it>0.007). Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion <it>in vitro</it>. <it>In vivo</it>, the average weight (<it>p </it>= 0.026) and volume (<it>p </it>= 0.044) of tumor in CNE-2/GFP<sup>+</sup>/Cripto-1<sup>- </sup>xenotransplant mice group were significantly lower than those in the control group. The Ki67 index was obviously lower in Cripto-1 RNAi treated tumors (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Data of this study suggest that Cripto-1 overexpression is connected with the tumorigenesis and progression of NPC, lentivector-mediated RNAi might be feasible for the inhibition of the growth and invasion of NPC.</p>
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spelling doaj.art-6daeed0c52294ce8ab9dcc92474790c72022-12-22T01:25:27ZengBMCBMC Cancer1471-24072009-09-019131510.1186/1471-2407-9-315Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinomaLi XiangpingWeng DeshengWu LirongLi GangWu ZhengrongYao Kaitai<p>Abstract</p> <p>Background</p> <p>Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines.</p> <p>Methods</p> <p>The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, <it>in vivo</it>, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument.</p> <p>Results</p> <p>The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17) cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37) cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (<it>p </it>= 0.034), distant metastasis (<it>p </it>= 0.036), and clinical stage (<it>p = </it>0.007). Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion <it>in vitro</it>. <it>In vivo</it>, the average weight (<it>p </it>= 0.026) and volume (<it>p </it>= 0.044) of tumor in CNE-2/GFP<sup>+</sup>/Cripto-1<sup>- </sup>xenotransplant mice group were significantly lower than those in the control group. The Ki67 index was obviously lower in Cripto-1 RNAi treated tumors (<it>p </it>< 0.01).</p> <p>Conclusion</p> <p>Data of this study suggest that Cripto-1 overexpression is connected with the tumorigenesis and progression of NPC, lentivector-mediated RNAi might be feasible for the inhibition of the growth and invasion of NPC.</p>http://www.biomedcentral.com/1471-2407/9/315
spellingShingle Li Xiangping
Weng Desheng
Wu Lirong
Li Gang
Wu Zhengrong
Yao Kaitai
Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
BMC Cancer
title Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
title_full Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
title_fullStr Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
title_full_unstemmed Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
title_short Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
title_sort cripto 1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma
url http://www.biomedcentral.com/1471-2407/9/315
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AT wulirong cripto1overexpressionisinvolvedinthetumorigenesisofnasopharyngealcarcinoma
AT ligang cripto1overexpressionisinvolvedinthetumorigenesisofnasopharyngealcarcinoma
AT wuzhengrong cripto1overexpressionisinvolvedinthetumorigenesisofnasopharyngealcarcinoma
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