Abstract
The Wnt signal transduction pathway regulates morphogenesis and mitogenesis of cells in multicellular organisms. A major downstream consequence of Wnt-1 signalling is the activation of beta-catenin/T-cell factor (TCF)-mediated transcription. We compared Wnt-1-transformed murine mammary epithelial cells with control cells by subtractive hybridization. We found the two genes Nr4a1 and Herpud1 to be overexpressed in Wnt-1-transformed cells. Remarkably, the transcription levels of the two homologous human genes NR4A1 and HERPUD1 are neither activated in cells with activated beta-catenin/TCF-mediated transcription nor can be induced by beta-catenin transfection. These results indicate different regulation mechanisms of the two genes in murine and human cells.
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- Behrens J., von Kries J. P., Kühl M., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996 Aug 15;382(6592):638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
- Bienz M., Clevers H. Linking colorectal cancer to Wnt signaling. Cell. 2000 Oct 13;103(2):311–320. doi: 10.1016/s0092-8674(00)00122-7. [DOI] [PubMed] [Google Scholar]
- Block C., Janknecht R., Herrmann C., Nassar N., Wittinghofer A. Quantitative structure-activity analysis correlating Ras/Raf interaction in vitro to Raf activation in vivo. Nat Struct Biol. 1996 Mar;3(3):244–251. doi: 10.1038/nsb0396-244. [DOI] [PubMed] [Google Scholar]
- Brattain M. G., Fine W. D., Khaled F. M., Thompson J., Brattain D. E. Heterogeneity of malignant cells from a human colonic carcinoma. Cancer Res. 1981 May;41(5):1751–1756. [PubMed] [Google Scholar]
- Chang C., Kokontis J., Liao S. S., Chang Y. Isolation and characterization of human TR3 receptor: a member of steroid receptor superfamily. J Steroid Biochem. 1989;34(1-6):391–395. doi: 10.1016/0022-4731(89)90114-3. [DOI] [PubMed] [Google Scholar]
- Crawford H. C., Fingleton B. M., Rudolph-Owen L. A., Goss K. J., Rubinfeld B., Polakis P., Matrisian L. M. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene. 1999 May 6;18(18):2883–2891. doi: 10.1038/sj.onc.1202627. [DOI] [PubMed] [Google Scholar]
- Dale T. C. Signal transduction by the Wnt family of ligands. Biochem J. 1998 Jan 15;329(Pt 2):209–223. doi: 10.1042/bj3290209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hazel T. G., Nathans D., Lau L. F. A gene inducible by serum growth factors encodes a member of the steroid and thyroid hormone receptor superfamily. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8444–8448. doi: 10.1073/pnas.85.22.8444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- He T. C., Chan T. A., Vogelstein B., Kinzler K. W. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999 Oct 29;99(3):335–345. doi: 10.1016/s0092-8674(00)81664-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- He T. C., Sparks A. B., Rago C., Hermeking H., Zawel L., da Costa L. T., Morin P. J., Vogelstein B., Kinzler K. W. Identification of c-MYC as a target of the APC pathway. Science. 1998 Sep 4;281(5382):1509–1512. doi: 10.1126/science.281.5382.1509. [DOI] [PubMed] [Google Scholar]
- Heinen C. D., Richardson D., White R., Groden J. Microsatellite instability in colorectal adenocarcinoma cell lines that have full-length adenomatous polyposis coli protein. Cancer Res. 1995 Nov 1;55(21):4797–4799. [PubMed] [Google Scholar]
- Howe L. R., Subbaramaiah K., Chung W. J., Dannenberg A. J., Brown A. M. Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells. Cancer Res. 1999 Apr 1;59(7):1572–1577. [PubMed] [Google Scholar]
- Hubank M., Schatz D. G. cDNA representational difference analysis: a sensitive and flexible method for identification of differentially expressed genes. Methods Enzymol. 1999;303:325–349. doi: 10.1016/s0076-6879(99)03021-9. [DOI] [PubMed] [Google Scholar]
- Jho Eek-hoon, Zhang Tong, Domon Claire, Joo Choun-Ki, Freund Jean-Noel, Costantini Frank. Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol. 2002 Feb;22(4):1172–1183. doi: 10.1128/MCB.22.4.1172-1183.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitagawa M., Hatakeyama S., Shirane M., Matsumoto M., Ishida N., Hattori K., Nakamichi I., Kikuchi A., Nakayama K., Nakayama K. An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO J. 1999 May 4;18(9):2401–2410. doi: 10.1093/emboj/18.9.2401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Korinek V., Barker N., Morin P. J., van Wichen D., de Weger R., Kinzler K. W., Vogelstein B., Clevers H. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997 Mar 21;275(5307):1784–1787. doi: 10.1126/science.275.5307.1784. [DOI] [PubMed] [Google Scholar]
- Lee H. J., Kokontis J., Wang K. C., Chang C. The use of a DNA-binding domain replacement method for the detection of a potential TR3 orphan receptor response element in the mouse mammary tumor virus long terminal repeat. Biochem Biophys Res Commun. 1993 Jul 15;194(1):97–103. doi: 10.1006/bbrc.1993.1790. [DOI] [PubMed] [Google Scholar]
- Leibovitz A., Stinson J. C., McCombs W. B., 3rd, McCoy C. E., Mazur K. C., Mabry N. D. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 1976 Dec;36(12):4562–4569. [PubMed] [Google Scholar]
- Li H., Kolluri S. K., Gu J., Dawson M. I., Cao X., Hobbs P. D., Lin B., Chen G., Lu J., Lin F. Cytochrome c release and apoptosis induced by mitochondrial targeting of nuclear orphan receptor TR3. Science. 2000 Aug 18;289(5482):1159–1164. doi: 10.1126/science.289.5482.1159. [DOI] [PubMed] [Google Scholar]
- Lustig Barbara, Jerchow Boris, Sachs Martin, Weiler Sigrid, Pietsch Torsten, Karsten Uwe, van de Wetering Marc, Clevers Hans, Schlag Peter M., Birchmeier Walter. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol. 2002 Feb;22(4):1184–1193. doi: 10.1128/MCB.22.4.1184-1193.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mann B., Gelos M., Siedow A., Hanski M. L., Gratchev A., Ilyas M., Bodmer W. F., Moyer M. P., Riecken E. O., Buhr H. J. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1603–1608. doi: 10.1073/pnas.96.4.1603. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Molenaar M., van de Wetering M., Oosterwegel M., Peterson-Maduro J., Godsave S., Korinek V., Roose J., Destrée O., Clevers H. XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996 Aug 9;86(3):391–399. doi: 10.1016/s0092-8674(00)80112-9. [DOI] [PubMed] [Google Scholar]
- Moon R. T., Kimelman D. From cortical rotation to organizer gene expression: toward a molecular explanation of axis specification in Xenopus. Bioessays. 1998 Jul;20(7):536–545. doi: 10.1002/(SICI)1521-1878(199807)20:7<536::AID-BIES4>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
- Morin P. J., Sparks A. B., Korinek V., Barker N., Clevers H., Vogelstein B., Kinzler K. W. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997 Mar 21;275(5307):1787–1790. doi: 10.1126/science.275.5307.1787. [DOI] [PubMed] [Google Scholar]
- Moyer M. P., Manzano L. A., Merriman R. L., Stauffer J. S., Tanzer L. R. NCM460, a normal human colon mucosal epithelial cell line. In Vitro Cell Dev Biol Anim. 1996 Jun;32(6):315–317. doi: 10.1007/BF02722955. [DOI] [PubMed] [Google Scholar]
- Nanni P., de Giovanni C., Lollini P. L., Nicoletti G., Prodi G. TS/A: a new metastasizing cell line from a BALB/c spontaneous mammary adenocarcinoma. Clin Exp Metastasis. 1983 Oct-Dec;1(4):373–380. doi: 10.1007/BF00121199. [DOI] [PubMed] [Google Scholar]
- Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement). DNA Res. 1994;1(1):47–56. doi: 10.1093/dnares/1.1.47. [DOI] [PubMed] [Google Scholar]
- Nusse R., Varmus H. E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982 Nov;31(1):99–109. doi: 10.1016/0092-8674(82)90409-3. [DOI] [PubMed] [Google Scholar]
- Nusse R. WNT targets. Repression and activation. Trends Genet. 1999 Jan;15(1):1–3. doi: 10.1016/s0168-9525(98)01634-5. [DOI] [PubMed] [Google Scholar]
- Pennica D., Swanson T. A., Welsh J. W., Roy M. A., Lawrence D. A., Lee J., Brush J., Taneyhill L. A., Deuel B., Lew M. WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14717–14722. doi: 10.1073/pnas.95.25.14717. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmann T., Jansson L. A novel pathway for vitamin A signaling mediated by RXR heterodimerization with NGFI-B and NURR1. Genes Dev. 1995 Apr 1;9(7):769–782. doi: 10.1101/gad.9.7.769. [DOI] [PubMed] [Google Scholar]
- Seidensticker M. J., Behrens J. Biochemical interactions in the wnt pathway. Biochim Biophys Acta. 2000 Feb 2;1495(2):168–182. doi: 10.1016/s0167-4889(99)00158-5. [DOI] [PubMed] [Google Scholar]
- Shimizu H., Julius M. A., Giarré M., Zheng Z., Brown A. M., Kitajewski J. Transformation by Wnt family proteins correlates with regulation of beta-catenin. Cell Growth Differ. 1997 Dec;8(12):1349–1358. [PubMed] [Google Scholar]
- Song K. H., Park J. I., Lee M. O., Soh J., Lee K., Choi H. S. LH induces orphan nuclear receptor Nur77 gene expression in testicular Leydig cells. Endocrinology. 2001 Dec;142(12):5116–5123. doi: 10.1210/endo.142.12.8525. [DOI] [PubMed] [Google Scholar]
- Stambolic V., Ruel L., Woodgett J. R. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 1996 Dec 1;6(12):1664–1668. doi: 10.1016/s0960-9822(02)70790-2. [DOI] [PubMed] [Google Scholar]
- Tao W., Pennica D., Xu L., Kalejta R. F., Levine A. J. Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev. 2001 Jul 15;15(14):1796–1807. doi: 10.1101/gad.894301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tetsu O., McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature. 1999 Apr 1;398(6726):422–426. doi: 10.1038/18884. [DOI] [PubMed] [Google Scholar]
- Vaidya A. B., Lasfargues E. Y., Sheffield J. B., Coutinho W. G. Murine mammary tumor virus (MuMTV) infection of an epithelial cell line established from C57BL/6 mouse mammary glands. Virology. 1978 Oct 1;90(1):12–22. doi: 10.1016/0042-6822(78)90328-8. [DOI] [PubMed] [Google Scholar]
- Walter I., Fleischmann M., Klein D., Müller M., Salmons B., Günzburg W. H., Renner M., Gelbmann W. Rapid and sensitive detection of enhanced green fluorescent protein expression in paraffin sections by confocal laser scanning microscopy. Histochem J. 2000 Feb;32(2):99–103. doi: 10.1023/a:1004014211408. [DOI] [PubMed] [Google Scholar]
- Young C. S., Kitamura M., Hardy S., Kitajewski J. Wnt-1 induces growth, cytosolic beta-catenin, and Tcf/Lef transcriptional activation in Rat-1 fibroblasts. Mol Cell Biol. 1998 May;18(5):2474–2485. doi: 10.1128/mcb.18.5.2474. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ziemer L. T., Pennica D., Levine A. J. Identification of a mouse homolog of the human BTEB2 transcription factor as a beta-catenin-independent Wnt-1-responsive gene. Mol Cell Biol. 2001 Jan;21(2):562–574. doi: 10.1128/MCB.21.2.562-574.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van Laar T., Schouten T., Hoogervorst E., van Eck M., van der Eb A. J., Terleth C. The novel MMS-inducible gene Mif1/KIAA0025 is a target of the unfolded protein response pathway. FEBS Lett. 2000 Mar 3;469(1):123–131. doi: 10.1016/s0014-5793(00)01253-9. [DOI] [PubMed] [Google Scholar]
- van der Heyden M. A., Rook M. B., Hermans M. M., Rijksen G., Boonstra J., Defize L. H., Destrée O. H. Identification of connexin43 as a functional target for Wnt signalling. J Cell Sci. 1998 Jun;111(Pt 12):1741–1749. doi: 10.1242/jcs.111.12.1741. [DOI] [PubMed] [Google Scholar]