Information de reference pour ce titreAccession Number: | 00006374-200524190-00004.
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Author: | Schimanski, Carl C 1,5; Schmitz, Gosta 1,5; Kashyap, Anuba 1; Bosserhoff, Anja K 2; Bataille, Frauke 2; Schafer, Stephan C 3; Lehr, Hans A 3; Berger, Martin R 4; Galle, Peter R 1; Strand, Susanne 1; Strand, Dennis *,1
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Institution: | (1)First Department of Internal Medicine, Johannes Gutenberg University, 55101 Mainz, Germany; (2)Institute of Pathology, University Regensburg, 93053 Regensburg, Germany; (3)Institute of Pathology, Johannes Gutenberg University, 55131 Mainz, Germany; (4)Unit of Toxicology and Chemotherapy, German Cancer Research Center, 69120 Heidelberg, Germany
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Title: | Reduced expression of Hugl-1, the human homologue of Drosophila tumour suppressor gene lgl, contributes to progression of colorectal cancer.[Article]
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Source: | Oncogene. 24(19):3100-3109, April 28, 2005.
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Abstract: | The human gene, human giant larvae (Hugl-1/Llg1/Lgl1) has significant homology to the Drosophila tumour suppressor gene lethal(2)giant larvae (lgl). The lgl gene codes for a cortical cytoskeleton protein, Lgl, that binds Myosin II and is involved in maintaining cell polarity and epithelial integrity. The human protein, Hugl-1 contains several conserved functional domains found in Lgl, suggesting that these proteins may have closely related functions. Whether loss of Hugl expression plays a role in human tumorigenesis has so far not been extensively investigated. Thus, we evaluated tumour tissues from 94 patients undergoing surgery for colorectal cancer (CRC) for loss of Hugl-1 transcription and compared our findings with the clinical data from each of these patients. We found that Hugl-1 was lost in 75% of tumour samples and these losses were associated with advanced stage and particularly with lymph node metastases. Reduced Hugl-1 expression during the adenoma-carcinoma sequence occurring as early as in colorectal adenomas was detected by both immunohistochemical and reverse transcription-polymerase chain reaction analysis. Functional assays with ecdysone-inducible cell lines revealed that Hugl-1 expression increased cell adhesion and decreased cell migration. Our studies thus indicate that downregulation of Hugl-1 contributes to CRC progression.
Copyright (C) 2005 Nature Publishing Group
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Author Keywords: | Lgl; Hugl-1; tumour suppressor; colon cancer.
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References: | Agrawal N, Kango M, Mishra A and Sinha P. (1995). Dev. Biol., 172, 218-229.
Boulay JL, Mild G, Reuter J, Lagrange M, Terracciano L, Lowy A, Laffer U, Orth B, Metzger U, Stamm B, Martinoli S, Herrmann R and Rochlitz C. (2001). Genes Chromosomes Cancer, 31, 240-247.
Chen KS, Gunaratne PH, Hoheisel JD, Young IG, Miklos GL, Greenberg F, Shaffer LG, Campbell HD and Lupski JR. (1995). Am. J. Hum. Genet., 56, 175-182.
Cho KR and Vogelstein B. (1992). Cancer, 70, 1727-1731.
Dow LE, Brumby AM, Muratore R, Coombe ML, Sedelies KA, Trapani JA, Russell SM, Richardson HE and Humbert PO. (2003). Oncogene, 22, 9225-9230.
Fuja TJ, Lin F, Osann KE and Bryant PJ. (2004). Cancer Res., 64, 942-951.
Gateff E. (1978). Science, 200, 1448-1459.
Grifoni D, Garoia F, Schimanski CC, Schmitz G, Laurenti E, Galle PR, Pession A, Cavicchi S and Strand D. (2004). Oncogene, 23, 8688-8694.
Guanti G and Bukvic N. (2000). Acta. Chir. Iugosl., 47, 23-25.
Houlston RS, Collins A, Slack J and Morton NE. (1992). Ann. Hum. Genet., 56 (Part 2), 99-103.
Humbert PO, Russell S and Richardson HE. (2003). BioEssays, 25, 542-553.
Ishidate T, Matsumine A, Toyoshima K and Akiyama T. (2000). Oncogene, 19, 365-372.
Kagami M, Toh-e A and Matusui Y. (1998). Genetics, 149, 1717-1727.
Klezovitch O, Fernandez TE, Tapscott SJ and Vasioukhin V. (2004). Genes Dev., 18, 559-571.
Koyama K, Fukushima Y, Inazawa J, Tomotsune D, Takahashi N and Nakamura Y. (1996). Cytogenet. Cell Genet., 72, 78-82.
Krishan A. (1975). J. Cell Biol., 66, 188-193.
Larsson K, Bohl F, Sjostrom I, Akhtar N, Strand D, Mechler BM, Grabowski R and Adler L. (1998). J. Biol. Chem., 273, 33610-33618.
Leslie A, Pratt NR, Gillespie K, Sales M, Kernohan NM, Smith G, Wolf CR and Carey FA. (2003). Cancer Res., 63, 4656-4661.
Lin HT, Steller MA, Aish L, Hanada T and Chishti AH. (2004). Gynecol. Oncol., 93, 422-428.
Micheli A, Mugno E, Krogh V, Quinn MJ, Coleman M, Hakulinen T, Gatta G, Berrino F and Capocaccia R. (2002). Ann. Oncol., 13, 840-865.
Nicoletti I, Migliorati G, Pagliacci MC, Grignani F and Riccardi C. (1991). J. Immunol. Methods, 139, 271-279.
Ohshiro T, Yagami T, Zhang C and Matsuzaki F. (2000). Nature, 408, 593-596.
Parker SL, Tong T, Bolden S and Wingo PA. (1996). CA Cancer J. Clin., 46, 5-27.
Parkin DM, Pisani P and Ferlay J. (1993). Int. J. Cancer, 54, 594-606.
Plant PJ, Fawcett JP, Lin DC, Holdorf AD, Binns K, Kulkarni S and Pawson T. (2003). Nat. Cell Biol., 5, 301-308.
Roth S, Johansson M, Loukola A, Peltomaki P, Jarvinen H, Mecklin JP and Aaltonen LA. (2000). J. Med. Genet., 37, 298-300.
Scheurlen WG, Seranski P, Mincheva A, Kuhl J, Sorensen N, Krauss J, Lichter P, Poustka A and Wilgenbus KK. (1997). Genes Chromosomes Cancer, 18, 50-58.
Scheurlen WG, Schwabe GC, Seranski P, Joos S, Harbott J, Metzke S, Dohner H, Poustka A, Wilgenbus KK and Haas OA. (1999). Genes Chromosomes Cancer, 25, 230-240.
Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ and Wolf CR. (2002). Proc. Natl. Acad. Sci. USA., 99, 9433-9438.
Strand D. (1998). G Proteins, Cytoskeleton and Cancer Maruta H, Kohama K. (eds). R.G. Landes: Georgetwon, TX, pp. 61-78.
Strand D, Jakobs R, Merdes G, Neumann B, Kalmes A, Heid HW, Husmann I and Mechler BM. (1994a). J. Cell Biol., 127, 1361-1373.
Strand D, Raska I and Mechler BM. (1994b). J. Cell Biol., 127, 1345-1360.
Strand D, Unger S, Corvi R, Hartenstein K, Schenkel H, Kalmes A, Merdes G, Neumann B, Krieg-Schneider F, Coy JF, Poustka A, Schwab M and Mechler BM. (1995). Oncogene, 11, 291-301.
Takagi Y, Koumura H, Futamura M, Aoki S, Ymaguchi K, Kida H, Tanemura H, Shimokawa K and Saji S. (1998). Br. J. Cancer, 78, 1152-1155.
Tanentzapf G and Tepass U. (2003). Nat. Cell Biol., 5, 46-52.
Thomas U, Phannavong B, Muller B, Garner CC and Gundelfinger ED. (1997). Mech. Dev., 62, 161-174.
Timmons L, Hersperger E, Woodhouse E, Xu J, Liu LZ and Shearn A. (1993). Dev. Biol., 158, 364-379.
Vogelstein B and Kinzler KW. (1993). Trends Genet., 9, 138-141.
Watson RA, Rollason TP, Reynolds GM, Murray PG, Banks L and Roberts S. (2002). Carcinogenesis, 23, 1791-1796.
Woodhouse E, Hersperger E and Shearn A. (1998). Dev. Genes Evol., 207, 542-550.
Woodhouse E, Hersperger E, Stetler-Stevenson WG, Liotta LA and Shearn A. (1994). Cell Growth Differ., 5, 151-159.
Yam JWP, Chan KW and Hsiao W. (2001). Oncogene, 20, 58-68.
Yamanaka T, Horikoshi Y, Sugiyama Y, Ishiyama C, Suzuki A, Hirose T, Iwamatsu A, Shinohara A and Ohno S. (2003). Curr. Biol., 13, 734-743.
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Language: | English.
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Document Type: | Original Papers.
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Journal Subset: | Clinical Medicine.
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ISSN: | 0950-9232
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NLM Journal Code: | onc, 8711562
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