[논문]초파리 대장조직과 인간 대장암세포주에서의 caudal 단백질에 의한 catalase 발현 조절

박재홍; 박소영; 이동호; 김영신; 유미애

doi:10.5352/jls.2011.21.2.194

초파리 대장조직과 인간 대장암세포주에서의 caudal 단백질에 의한 catalase 발현 조절
The Caudal-Related Homeodomain Proteins Upregulate catalase Expression in Drosophila Hindgut and Human Colorectal Carcinoma Cells 원문보기

생명과학회지 = Journal of life science, v.21 no.2 = no.130, 2011년, pp.194 - 201

박재홍 (부산대학교 분자생물학과) , 박소영 (부산대학교 분자생물학과) , 이동호 (부산대학교 분자생물학과) , 김영신 (부산대학교 유전공학연구소) , 유미애 (부산대학교 분자생물학과)

초록
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Caudal homeodomain 단백질은 초파리에서 사람에 이르기까지 보존되어 있으며, 장조직의 발생과 유지에 필수적인 역할을 한다. CDX1과 CDX2의 발현 감소 혹은 소실이 대장암과 연관되어 있음이 잘 알려져 있다. 대장암 발생은 산화성 스트레스와 밀접한 관련이 있으며, 대장암 조직에서 항산화효소인 catalase의 발현이 감소되어 있다. 하지만 그 분자적 기전은 잘 밝혀져 있지 않다. 본 연구에서는 초파리와 사람의 caudal homeodomain 단백질들이 catalase의 발현을 조절하는 것을 보여준다. 초파리 caudal heterozygous 돌연변이체의 대장조직에서 catalase의 발현이 감소되어 있고 ROS 생성이 증가되어 있음을 관찰하였다. 그리고 caudal 유전자의 과발현에 의해 catalase promoter의 활성과 mRNA 수준이 각각 증가함을 확인하였다. 또한 사람의 대장암 세포주인 HCT116 세포에서 CDX1과 CDX2가 catalase promoter의 활성과 단백질 수준에서 catalase를 상향 조절함을 관찰하였다. 이러한 결과들은 CDX1과 CDX2가 catalase 발현 조절을 통하여 장의 항상성 유지와 암발생 과정에 관여함을 시사한다.

Abstract ▼ AI-Helper

Caudal-related homeodomain proteins play critical roles in intestine development and maintenance from Drosophila to humans. The loss or reduction of CDX1 and CDX2 are known to be associated with colon cancers. It has been well known that colorectal carcinogenesis is associated with serious oxidative stress and that catalase is decreased in colon carcinomas. However, the underlying molecular mechanisms remain elusive. Here, we report that Caudal-related homeodomain proteins positively regulate catalase expression in both Drosophila and humans. We found that Drosophila caudal heterozygotes have a decreased catalase expression and increased ROS generation in the hindgut, and that the overexpression of Caudal increases catalase promoter activity and catalase mRNA levels. We also found that CDX1 and CDX2 up-regulate catalase promoter activity and protein levels in HCT116 cells - human colorectal carcinoma cell lines. The level of catalase protein in several colorectal carcinoma cell lines was associated with CDX1 expression. These results suggest that CDX1 and CDX2 may be involved in intestinal homeostasis and tumorigenesis via regulation of catalase expression.

주제어

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가설 설정

Expression of b-galactosidase in the hindgut was decreased by cad3 allele. (B) Quantitative b-galactosidase activities of the hindgut of wild type and cad3 heterozygous adult flies. The adult hindgut extracts were prepared from 3-day-old adult transgenic flies as described in Materials and Methods.

제안 방법

Normalized luciferase activities were calculated by determining the luciferase/ β-galactosidase activity ratios, and reported as the mean±S.D. from triplicate transfections.

성능/효과

Evidences have been given in some reports that H 2O 2 could promote cell growth and related gene expression in human tumors such as breast cancer and colon cancer [17,31,42]. From these facts, our results suggest that loss or reduction of CDX1 and/or CDX2 causes decreased expression of Catalase, which may increase oxidative stress in colon, accumulate genetic alterations and induce tumorigenesis.
4A). To confirm whether Catalase promoter activity is regulated by CDX1 and CDX2, phCat-Luc was transfected into CDX1 and CDX2 stable transfectants, respectively. The luciferase activities in the HCT-CDX1 and in the HCT-CDX2 cell lines were 9- to 11-fold and 4-fold of the HCT-pcDNA3, respectively (Fig.

참고문헌 (42)

Albuszies, G. and U. B. Bruckner. 2003. Antioxidant therapy in sepsis. Intensive Care Med. 29, 1632-1636.

상세보기
Almeida, R., E. Silva, F. Santos-Silva, D. G. Silberg, J. Wang, C. De Bolos, and L. David. 2003. Expression of intestine- specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. J. Pathol. 199, 36-40.

상세보기
Baba Y., K. Nosho, K. Shima, E. Freed, N. Irahara, J. Philips, J. A. Meyerhardt, J. L. Hornick, R. A. Shivdasani, C. S. Fuchs, and S. Ogino. 2009. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin. Cancer Res. 15, 4665-4673.

상세보기
Bartsch, H., J. Nair, and R. W. Owen. 2002. Exocyclic DNA adducts as oxidative stress markers in colon carcinogenesis: potential role of lipid peroxidation, dietary fat and antioxidants. Biol. Chem. 383, 915-921.

상세보기
Butler, H., S. Levine, X. Wang, S. Bonyadi, G. Fu, P. Lasko, B. Suter, and R. Doerig. 2001. Map position and expression of the genes in the 38 region of Drosophila. Genetics 158, 1597-1614.

상세보기
Chawengsaksophak, K., R. James, V. E. Hammond, F. Kontgen, and F. Beck. 1997. Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 386, 84-87.

상세보기
Choi, Y. J., T. Y. Choi, M. Yamaguchi, A. Matsukage, Y. S. Kim, and M. A. Yoo. 2004. Transcriptional regulation of the Drosophila caudal homeobox gene by DRE/DREF. Nucleic Acids Res. 32, 3734-3742.

상세보기
Crissey, M. A., R. J. Guo, S. Funakoshi, J. Kong, J. Liu, and J. P. Lynch. 2010. Cdx2 levels modulate intestinal epithelium maturity and Paneth cell development. Gastroenterology 140, 517-528.
Cuzzocrea, S., D. P. Riley, A. P. Caputi, and D. Salvemini. 2001. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol. Rev. 53, 135-159.

상세보기
Domon-Dell, C., A. Schneider, V. Moucadel, E. Guerin, D. Guenot, S. Aguillon, I. Duluc, E. Martin, J. Iovanna, J. F. Launay, B. Duclos, M. P. Chenard, C. Meyer, P. Oudet, M. Kedinger, M. P. Gaub, and J. N. Freund. 2003. Cdx1 homeobox gene during human colon cancer progression. Oncogene 22, 7913-7921.

상세보기
Fischer, J. A., E. Giniger, T. Maniatis, and M. Ptashne. 1988. GAL4 activates transcription in Drosophila. Nature 332, 853-856.

상세보기
Gupta, A., S. F. Rosenberger, and G. T. Bowden. 1999. Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines. Carcinogenesis 20, 2063-2073.

상세보기
Han, K. 1996. An efficient DDAB-mediated transfection of Drosophila S2 cells. Nucleic Acids Res. 24, 4362-4363.

상세보기
Hunt, C. R., J. E. Sim, S. J. Sullivan, T. Featherstone, W. Golden, C. Von Kapp-Herr, R. A. Hock, R. A. Gomez, A. J. Parsian, and D. R. Spitz. 1998. Genomic instability and catalase gene amplification induced by chronic exposure to oxidative stress. Cancer Res. 58, 3986-3992.

상세보기
Hwang, M. S., Y. S. Kim, N. H. Choi, J. H. Park, E. J. Oh, E. J Kwon, M. Yamaguchi, and M. A. Yoo. 2002. The caudal homeodomain protein activates Drosophila E2F gene expression. Nucleic Acids Res. 30, 5029-5035.

상세보기
Jackson, A. L. and L. A. Loeb. 2001. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat. Res. 477, 7-21.

상세보기
Joseph, P., T. K. Muchnok, M. L. Klishis, J. R. Roberts, J. M. Antonini, W. Z. Whong, and T. Ong. 2001. Cadmium-induced cell transformation and tumorigenesis are associated with transcriptional activation of c-fos, c-jun, and c-myc proto-oncogenes: role of cellular calcium and reactive oxygen species. Toxicol. Sci. 61, 295-303.

상세보기
Kessel, M. and P. Gruss. 1990. Murine developmental control genes. Science 249, 374-379.

상세보기
Kim, H. S., T. B. Lee, and C. H. Choi. 2001. Down-regulation of catalase gene expression in the doxorubicin-resistant AML subline AML-2/DX100. Biochem. Biophys. Res. Commun. 281, 109-114.

상세보기
Kuhnlein, R. P., G. Bronner, H. Taubert, and R. Schuh. 1997. Regulation of Drosophila spalt gene expression. Mech. Dev. 66, 107-118.

상세보기
Lauer, C., A. Volkl, S. Riedl, H. D. Fahimi, and K. Beier. 1999. Impairment of peroxisomal biogenesis in human colon carcinoma. Carcinogenesis 20, 985-989.

상세보기
Lewis, A. D., I. D. Hickson, C. N. Robson, A. L. Harris, J. D. Hayes, S. A. Griffiths, M. M. Manson, A. E. Hall, J. E. Moss, and C. R. Wolf. 1988. Amplification and increased expression of alpha class glutathione S-transferase-encoding genes associated with resistance to nitrogen mustards. Proc. Natl. Acad. Sci. USA 85, 8511- 8515.

상세보기
Lewis, M. T. 2000. Homeobox genes in mammary gland development and neoplasia. Breast Cancer Res. 2, 158-169.

상세보기
Luo, D. and T. A. Rando. 2003. The regulation of catalase gene expression in mouse muscle cells is dependent on the CCAAT-binding factor NF-Y. Biochem. Biophys. Res. Commun. 303, 609-618.

상세보기
Mallo, G. V., H. Rechreche, J. M. Frigerio, D. Rocha, A. Zweibaum, M. Lacasa, B. R. Jordan, N. J. Dusetti, J. C. Dagorn, and J. L. Iovanna. 1997. Molecular cloning, sequencing and expression of the mRNA encoding human Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression during colorectal carcinogenesis. Int. J. Cancer 74, 35-44.

상세보기
McGinnis, W. and R. Krumlauf. 1992. Homeobox genes and axial patterning. Cell 68, 283-302.

상세보기
Michiels, C., M. Raes, O. Toussaint, and J. Remacle. 1994. Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic. Biol. Med. 17, 235-248.

상세보기
Nenoi, M., S. Ichimura, K. Mita, O. Yukawa, and I. L. Cartwright. 2001. Regulation of the catalase gene promoter by Sp1, CCAAT-recognizing factors, and a WT1/Egr-related factor in hydrogen peroxide-resistant HP100 cells. Cancer Res. 61, 5885-5894.

상세보기
Park, S. Y., Y.S. Kim, D. J. Yang, and M. A. Yoo. 2004. Transcriptional regulation of the Drosophila catalase gene by the DRE/DREF system. Nucleic Acids Res. 32, 1318-1324.

상세보기
Ren, P., D. G. Silberg, and A. E. Sirica. 2000. Expression of an intestine-specific transcription factor (CDX1) in intestinal metaplasia and in subsequently developed intestinal type of cholangiocarcinoma in rat liver. Am. J. Pathol. 156, 621-627.

상세보기
Rhee, S. G. 1999. Redox signaling: hydrogen peroxide as intracellular messenger. Exper. Mol. Med. 35, 53-59.
Sanders, L. M., C. E. Henderson, M. Y. Hong, R. Barhoumi, R. C. Burghardt, N. Wang, C. M. Spinka, R. J. Carroll, N. D. Turner, R. S. Chapkin, and J. R. Lupton. 2004. An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis. J. Nutr. 134, 3233-3238.

상세보기
Silberg, D. G., G. P. Swain, E. R. Suh, and P. G. Traber. 2000. Cdx1 and Cdx2 expression during intestinal development. Gastroenterology 119, 961-971.

상세보기
Skrzydlewska, E., S. Sulkowski, M. Koda, B. Zalewski, L. Kanczuga-Koda, and M. Sulkowska. 2005. Lipid peroxidation and antioxidant status in colorectal cancer. World J. Gastroenterol. 11, 403-406.

상세보기
Tsutsumishita, Y., T. Onda, K. Okada, M. Takeda, H. Endou, S. Futaki, and M. Niwa. 1998. Involvement of $H_2O_2$ production in cisplatin-induced nephrotoxicity. Biochem. Biophys. Res. Commun. 242, 310-312.

상세보기
Van Remmen, H., M. D. Williams, H. Yang, C. A. Walter, and A. Richardson. 1998. Analysis of the transcriptional activity of the 5'-flanking region of the rat catalase gene in transiently transfected cells and in transgenic mice. J. Cell Physiol. 174, 18-26.

상세보기
Wang, W. W., D. L. Smith, and S. D. Zucker. 2004. Bilirubin inhibits iNOS expression and NO production in response to endotoxin in rats. Hepatology 40, 424-433.
Werling, R. W., H. Yaziji, C. E. Bacchi, and A. M. Gown. 2003. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am. J. Surg. Pathol. 27, 303-310.

상세보기
de Winter, B. Y., L. van Nassauw, J. G. de Man, F. de Jonge, A. J. Bredenoord, T. C. Seerden, A. G. Herman, J. P. Timmermans, and P. A. Pelckmans. 2005. Role of oxidative stress in the pathogenesis of septic ileus in mice. Neurogastroenterol. Motil. 17, 251-261.

상세보기
Wong, N. A., M. P. Britton, G. S. Choi, T. K. Stanton, D. C. Bicknell, J. L. Wilding, and W. F. Bodmer. 2004. Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines. Proc. Natl. Acad. Sci. USA 101, 574-579.

상세보기
Wu, L. H. and J. A. Lengyel. 1998. Role of caudal in hindgut specification and gastrulation suggests homology between Drosophila amnioproctodeal invagination and vertebrate blastopore. Development 125, 2433-2442.
Zhu, J. W., B. M. Yu, Y. B. Ji, M H. Zheng, and D. H. Li. 2002. Upregulation of vascular endothelial growth factor by hydrogen peroxide in human colon cancer. World J. Gastroenterol. 8, 153-157.

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