NDRG2 expression decreases with tumor stages and regulates TCF/ β-catenin signaling in human colon carcinoma

Young Jun Kim, Sun Y. Yoon, Jong Tae Kim, Eun Y. Song, Hee G. Lee, Hyun J. Son, Soo Y. Kim, Dae Ho Cho, Inpyo Choi, Joo Heon Kim, Jae W. Kim

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Abstract

NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2 -expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular β-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of β-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/β-catenin signaling for the maintenance of healthy colon tissues.

Original languageEnglish
Pages (from-to)598-605
Number of pages8
JournalCarcinogenesis
Volume30
Issue number4
DOIs
Publication statusPublished - 2009 Apr 17
Externally publishedYes

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TCF Transcription Factors
Catenins
Colon
Carcinoma
Neoplasms
Immunologic Suppressor Factors
Glycogen Synthase Kinases
Cell Line
Site-Directed Mutagenesis
Luciferases
Colonic Neoplasms
Genes
Reverse Transcription
Carcinogenesis
Mucous Membrane
Adenocarcinoma
Plasmids
Cell Culture Techniques
Monoclonal Antibodies
Maintenance

ASJC Scopus subject areas

  • Cancer Research

Cite this

Kim, Y. J., Yoon, S. Y., Kim, J. T., Song, E. Y., Lee, H. G., Son, H. J., ... Kim, J. W. (2009). NDRG2 expression decreases with tumor stages and regulates TCF/ β-catenin signaling in human colon carcinoma. Carcinogenesis, 30(4), 598-605. https://doi.org/10.1093/carcin/bgp047

NDRG2 expression decreases with tumor stages and regulates TCF/ β-catenin signaling in human colon carcinoma. / Kim, Young Jun; Yoon, Sun Y.; Kim, Jong Tae; Song, Eun Y.; Lee, Hee G.; Son, Hyun J.; Kim, Soo Y.; Cho, Dae Ho; Choi, Inpyo; Kim, Joo Heon; Kim, Jae W.

In: Carcinogenesis, Vol. 30, No. 4, 17.04.2009, p. 598-605.

Research output: Contribution to journalArticle

Kim, YJ, Yoon, SY, Kim, JT, Song, EY, Lee, HG, Son, HJ, Kim, SY, Cho, DH, Choi, I, Kim, JH & Kim, JW 2009, 'NDRG2 expression decreases with tumor stages and regulates TCF/ β-catenin signaling in human colon carcinoma', Carcinogenesis, vol. 30, no. 4, pp. 598-605. https://doi.org/10.1093/carcin/bgp047
Kim, Young Jun ; Yoon, Sun Y. ; Kim, Jong Tae ; Song, Eun Y. ; Lee, Hee G. ; Son, Hyun J. ; Kim, Soo Y. ; Cho, Dae Ho ; Choi, Inpyo ; Kim, Joo Heon ; Kim, Jae W. / NDRG2 expression decreases with tumor stages and regulates TCF/ β-catenin signaling in human colon carcinoma. In: Carcinogenesis. 2009 ; Vol. 30, No. 4. pp. 598-605.
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AU - Lee, Hee G.

AU - Son, Hyun J.

AU - Kim, Soo Y.

AU - Cho, Dae Ho

AU - Choi, Inpyo

AU - Kim, Joo Heon

AU - Kim, Jae W.

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AB - NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2 -expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular β-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of β-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/β-catenin signaling for the maintenance of healthy colon tissues.

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