This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wong, G T
Right arrow Articles by McMahon, A P
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wong, G T
Right arrow Articles by McMahon, A P

 Previous Article  |  Next Article 

Mol Cell Biol. 1994 September; 14(9): 6278-6286

Differential transformation of mammary epithelial cells by Wnt genes.

G T Wong, B J Gavin and A P McMahon

Roche Institute of Molecular Biology, Nutley, New Jersey 07110.

ABSTRACT

The mouse Wnt family includes at least 10 genes that encode structurally related secreted glycoproteins. Wnt-1 and Wnt-3 were originally identified as oncogenes activated by the insertion of mouse mammary tumor virus in virus-induced mammary adenocarcinomas, although they are not expressed in the normal mammary gland. However, five other Wnt genes are differentially expressed during development of adult mammary tissue, suggesting that they may play distinct roles in various phases of mammary gland growth and development. Induction of transformation by Wnt-1 and Wnt-3 may be due to interference with these normal regulatory events; however, there is no direct evidence for this hypothesis. We have tested Wnt family members for the ability to induce transformation of cultured mammary cells. The results demonstrate that the Wnt gene family can be divided into three groups depending on their ability to induce morphological transformation and altered growth characteristics of the C57MG mammary epithelial cell line. Wnt-1, Wnt-3A, and Wnt-7A were highly transforming and induced colonies which formed and shed balls of cells. Wnt-2, Wnt-5B, and Wnt-7B also induced transformation but with a lower frequency and an apparent decrease in saturation density. In contrast, Wnt-6 and two other family members which are normally expressed in C57MG cells, Wnt-4 and Wnt-5A, failed to induce transformation. These data demonstrate that the Wnt genes have distinct effects on cell growth and should not be regarded as functionally equivalent.

Mol Cell Biol. 1994 September; 14(9): 6278-6286




This article has been cited by other articles:

  • van Amerongen, R., Nusse, R. (2009). Towards an integrated view of Wnt signaling in development. Development 136: 3205-3214 [Abstract] [Full Text]  
  • Muraoka-Cook, R. S., Sandahl, M. A., Strunk, K. E., Miraglia, L. C., Husted, C., Hunter, D. M., Elenius, K., Chodosh, L. A., Earp, H. S. III (2009). ErbB4 Splice Variants Cyt1 and Cyt2 Differ by 16 Amino Acids and Exert Opposing Effects on the Mammary Epithelium In Vivo. Mol. Cell. Biol. 29: 4935-4948 [Abstract] [Full Text]  
  • Schwartz, A. L., Malgor, R., Dickerson, E., Weeraratna, A. T., Slominski, A., Wortsman, J., Harii, N., Kohn, A. D., Moon, R. T., Schwartz, F. L., Goetz, D. J., Kohn, L. D., McCall, K. D. (2009). Phenylmethimazole Decreases Toll-Like Receptor 3 and Noncanonical Wnt5a Expression in Pancreatic Cancer and Melanoma Together with Tumor Cell Growth and Migration. Clin. Cancer Res. 15: 4114-4122 [Abstract] [Full Text]  
  • Adell, T., Salo, E., Boutros, M., Bartscherer, K. (2009). Smed-Evi/Wntless is required for {beta}-catenin-dependent and -independent processes during planarian regeneration. Development 136: 905-910 [Abstract] [Full Text]  
  • Yokota, T., Oritani, K., Garrett, K. P., Kouro, T., Nishida, M., Takahashi, I., Ichii, M., Satoh, Y., Kincade, P. W., Kanakura, Y. (2008). Soluble Frizzled-Related Protein 1 Is Estrogen Inducible in Bone Marrow Stromal Cells and Suppresses the Earliest Events in Lymphopoiesis. J. Immunol. 181: 6061-6072 [Abstract] [Full Text]  
  • van Amerongen, R., Mikels, A., Nusse, R. (2008). Alternative Wnt Signaling Is Initiated by Distinct Receptors. Sci Signal 1: re9-re9 [Abstract] [Full Text]  
  • Cohen, E. D., Tian, Y., Morrisey, E. E. (2008). Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal. Development 135: 789-798 [Abstract] [Full Text]  
  • Ying, J., Li, H., Yu, J., Ng, K. M., Poon, F. F., Wong, S. C. C., Chan, A. T.C., Sung, J. J.Y., Tao, Q. (2008). WNT5A Exhibits Tumor-Suppressive Activity through Antagonizing the Wnt/ -Catenin Signaling, and Is Frequently Methylated in Colorectal Cancer. Clin. Cancer Res. 14: 55-61 [Abstract] [Full Text]  
  • Liang, H., Coles, A. H., Zhu, Z., Zayas, J., Jurecic, R., Kang, J., Jones, S. N. (2007). Noncanonical Wnt signaling promotes apoptosis in thymocyte development. JEM 204: 3077-3084 [Abstract] [Full Text]  
  • Ying, J., Li, H., Chen, Y.-W., Srivastava, G., Gao, Z., Tao, Q. (2007). WNT5A is epigenetically silenced in hematologic malignancies and inhibits leukemia cell growth as a tumor suppressor. Blood 110: 4130-4131 [Full Text]  
  • McCall, K. D., Harii, N., Lewis, C. J., Malgor, R., Bae Kim, W., Saji, M., Kohn, A. D., Moon, R. T., Kohn, L. D. (2007). High Basal Levels of Functional Toll-Like Receptor 3 (TLR3) and Noncanonical Wnt5a Are Expressed in Papillary Thyroid Cancer and Are Coordinately Decreased by Phenylmethimazole Together with Cell Proliferation and Migration. Endocrinology 148: 4226-4237 [Abstract] [Full Text]  
  • Kuorelahti, A., Rulli, S., Huhtaniemi, I., Poutanen, M. (2007). Human Chorionic Gonadotropin (hCG) Up-Regulates wnt5b and wnt7b in the Mammary Gland, and hCG{beta} Transgenic Female Mice Present with Mammary Gland Tumors Exhibiting Characteristics of the Wnt/{beta}-Catenin Pathway Activation. Endocrinology 148: 3694-3703 [Abstract] [Full Text]  
  • Ripka, S, Konig, A, Buchholz, M, Wagner, M, Sipos, B, Kloppel, G, Downward, J, Gress, T., Michl, P (2007). WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion in pancreatic cancer. Carcinogenesis 28: 1178-1187 [Abstract] [Full Text]  
  • Kurayoshi, M., Oue, N., Yamamoto, H., Kishida, M., Inoue, A., Asahara, T., Yasui, W., Kikuchi, A. (2006). Expression of Wnt-5a Is Correlated with Aggressiveness of Gastric Cancer by Stimulating Cell Migration and Invasion. Cancer Res. 66: 10439-10448 [Abstract] [Full Text]  
  • Pukrop, T., Klemm, F., Hagemann, Th., Gradl, D., Schulz, M., Siemes, S., Trumper, L., Binder, C. (2006). Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines. Proc. Natl. Acad. Sci. USA 103: 5454-5459 [Abstract] [Full Text]  
  • Blavier, L., Lazaryev, A., Dorey, F., Shackleford, G. M., DeClerck, Y. A. (2006). Matrix metalloproteinases play an active role in wnt1-induced mammary tumorigenesis.. Cancer Res. 66: 2691-2699 [Abstract] [Full Text]  
  • Yun, M.-S., Kim, S.-E., Jeon, S. H., Lee, J.-S., Choi, K.-Y. (2005). Both ERK and Wnt/{beta}-catenin pathways are involved in Wnt3a-induced proliferation. J. Cell Sci. 118: 313-322 [Abstract] [Full Text]  
  • Lyu, J., Joo, C.-K. (2004). Wnt signaling enhances FGF2-triggered lens fiber cell differentiation. Development 131: 1813-1824 [Abstract] [Full Text]  
  • Strutt, D. (2003). Frizzled signalling and cell polarisation in Drosophila and vertebrates. Development 130: 4501-4513 [Abstract] [Full Text]  
  • Ohira, T., Gemmill, R. M., Ferguson, K., Kusy, S., Roche, J., Brambilla, E., Zeng, C., Baron, A., Bemis, L., Erickson, P., Wilder, E., Rustgi, A., Kitajewski, J., Gabrielson, E., Bremnes, R., Franklin, W., Drabkin, H. A. (2003). WNT7a induces E-cadherin in lung cancer cells. Proc. Natl. Acad. Sci. USA 100: 10429-10434 [Abstract] [Full Text]  
  • Ishitani, T., Kishida, S., Hyodo-Miura, J., Ueno, N., Yasuda, J., Waterman, M., Shibuya, H., Moon, R. T., Ninomiya-Tsuji, J., Matsumoto, K. (2003). The TAK1-NLK Mitogen-Activated Protein Kinase Cascade Functions in the Wnt-5a/Ca2+ Pathway To Antagonize Wnt/{beta}-Catenin Signaling. Mol. Cell. Biol. 23: 131-139 [Abstract] [Full Text]  
  • You, Z., Saims, D., Chen, S., Zhang, Z., Guttridge, D. C., Guan, K.-l., MacDougald, O. A., Brown, A. M.C., Evan, G., Kitajewski, J., Wang, C.-Y. (2002). Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced apoptosis. JCB 157: 429-440 [Abstract] [Full Text]  
  • Tice, D. A., Szeto, W., Soloviev, I., Rubinfeld, B., Fong, S. E., Dugger, D. L., Winer, J., Williams, P. M., Wieand, D., Smith, V., Schwall, R. H., Pennica, D., Polakis, P. (2002). Synergistic Induction of Tumor Antigens by Wnt-1 Signaling and Retinoic Acid Revealed by Gene Expression Profiling. J. Biol. Chem. 277: 14329-14335 [Abstract] [Full Text]  
  • Jonsson, M., Dejmek, J., Bendahl, P.-O., Andersson, T. (2002). Loss of Wnt-5a Protein Is Associated with Early Relapse in Invasive Ductal Breast Carcinomas. Cancer Res. 62: 409-416 [Abstract] [Full Text]  
  • Hsu, W., Shakya, R., Costantini, F. (2001). Impaired mammary gland and lymphoid development caused by inducible expression of Axin in transgenic mice. JCB 155: 1055-1064 [Abstract] [Full Text]  
  • Helmbrecht, K., Kispert, A., von Wasielewski, R., Brabant, G. (2001). Identification of a Wnt/{beta}-Catenin Signaling Pathway in Human Thyroid Cells. Endocrinology 142: 5261-5266 [Abstract] [Full Text]  
  • Szeto, W., Jiang, W., Tice, D. A., Rubinfeld, B., Hollingshead, P. G., Fong, S. E., Dugger, D. L., Pham, T., Yansura, D. G., Wong, T. A., Grimaldi, J. C., Corpuz, R. T., Singh, J. S., Frantz, G. D., Devaux, B., Crowley, C. W., Schwall, R. H., Eberhard, D. A., Rastelli, L., Polakis, P., Pennica, D. (2001). Overexpression of the Retinoic Acid-responsive Gene Stra6 in Human Cancers and Its Synergistic Induction by Wnt-1 and Retinoic Acid. Cancer Res. 61: 4197-4205 [Abstract] [Full Text]  
  • Chen, S., Guttridge, D. C., You, Z., Zhang, Z., Fribley, A., Mayo, M. W., Kitajewski, J., Wang, C.-Y. (2001). WNT-1 Signaling Inhibits Apoptosis by Activating {beta}-Catenin/T Cell Factor-Mediated Transcription. JCB 152: 87-96 [Abstract] [Full Text]  
  • Polakis, P. (2000). Wnt signaling and cancer. Genes Dev. 14: 1837-1851 [Full Text]  
  • Toyofuku, T., Hong, Z., Kuzuya, T., Tada, M., Hori, M. (2000). WNT/Frizzled-2 Signaling Induces Aggregation and Adhesion among Cardiac Myocytes by Increased Cadherin-{beta}-Catenin Complex. JCB 150: 225-242 [Abstract] [Full Text]  
  • Kuhl, M., Sheldahl, L. C., Malbon, C. C., Moon, R. T. (2000). Ca2+/Calmodulin-dependent Protein Kinase II Is Stimulated by Wnt and Frizzled Homologs and Promotes Ventral Cell Fates in Xenopus. J. Biol. Chem. 275: 12701-12711 [Abstract] [Full Text]  
  • Charpentier, E., Lavker, R. M., Acquista, E., Cowin, P. (2000). Plakoglobin Suppresses Epithelial Proliferation and Hair Growth in Vivo. JCB 149: 503-520 [Abstract] [Full Text]  
  • Robinson, G. W., Hennighausen, L., Johnson, P. F. (2000). Side-branching in the mammary gland: the progesterone-Wnt connection. Genes Dev. 14: 889-894 [Full Text]  
  • Hartmann, C, Tabin, C. (2000). Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127: 3141-3159 [Abstract]  
  • Naylor, S, Smalley, M., Robertson, D, Gusterson, B., Edwards, P., Dale, T. (2000). Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium. J. Cell Sci. 113: 2129-2138 [Abstract]  
  • Moriguchi, T., Kawachi, K., Kamakura, S., Masuyama, N., Yamanaka, H., Matsumoto, K., Kikuchi, A., Nishida, E. (1999). Distinct Domains of Mouse Dishevelled Are Responsible for the c-Jun N-terminal Kinase/Stress-activated Protein Kinase Activation and the Axis Formation in Vertebrates. J. Biol. Chem. 274: 30957-30962 [Abstract] [Full Text]  
  • Fedi, P., Bafico, A., Soria, A. N., Burgess, W. H., Miki, T., Bottaro, D. P., Kraus, M. H., Aaronson, S. A. (1999). Isolation and Biochemical Characterization of the Human Dkk-1 Homologue, a Novel Inhibitor of Mammalian Wnt Signaling. J. Biol. Chem. 274: 19465-19472 [Abstract] [Full Text]  
  • Bafico, A., Gazit, A., Pramila, T., Finch, P. W., Yaniv, A., Aaronson, S. A. (1999). Interaction of Frizzled Related Protein (FRP) with Wnt Ligands and the Frizzled Receptor Suggests Alternative Mechanisms for FRP Inhibition of Wnt Signaling. J. Biol. Chem. 274: 16180-16187 [Abstract] [Full Text]  
  • Yamamoto, H., Kishida, S., Kishida, M., Ikeda, S., Takada, S., Kikuchi, A. (1999). Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3beta Regulates Its Stability. J. Biol. Chem. 274: 10681-10684 [Abstract] [Full Text]  
  • Schulz, R., Wehmeyer, A., Schulz, K., Murphy, J. (1999). Effect of Phosducin on Opioid Receptor Function. J. Pharmacol. Exp. Ther. 289: 599-606 [Abstract] [Full Text]  
  • Dennis, S, Aikawa, M, Szeto, W, d'Amore, P., Papkoff, J (1999). A secreted frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates wnt-1 signaling. J. Cell Sci. 112: 3815-3820 [Abstract]  
  • 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., Watanabe, C., Cohen, R. L., Melhem, M. F., Finley, G. G., Quirke, P., Goddard, A. D., Hillan, K. J., Gurney, A. L., Botstein, D., Levine, A. J. (1998). 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. USA 95: 14717-14722 [Abstract] [Full Text]  
  • Van Den Berg, D. J., Sharma, A. K., Bruno, E., Hoffman, R. (1998). Role of Members of the Wnt Gene Family in Human Hematopoiesis. Blood 92: 3189-3202 [Abstract] [Full Text]  
  • Axelrod, J. D., Miller, J. R., Shulman, J. M., Moon, R. T., Perrimon, N. (1998). Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. Genes Dev. 12: 2610-2622 [Abstract] [Full Text]  
  • Kengaku, M., Capdevila, J., Rodriguez-Esteban, C., De La Peña, J., Johnson, R. L., Belmonte, J. C. I., Tabin, C. J. (1998). Distinct WNT Pathways Regulating AER Formation and Dorsoventral Polarity in the Chick Limb Bud. Science 280: 1274-1277 [Abstract] [Full Text]  
  • Young, C. S., Kitamura, M., Hardy, S., Kitajewski, J. (1998). Wnt-1 Induces Growth, Cytosolic beta -Catenin, and Tcf/Lef Transcriptional Activation in Rat-1 Fibroblasts. Mol. Cell. Biol. 18: 2474-2485 [Abstract] [Full Text]  
  • Korinek, V., Barker, N., Willert, K., Molenaar, M., Roose, J., Wagenaar, G., Markman, M., Lamers, W., Destree, O., Clevers, H. (1998). Two Members of the Tcf Family Implicated in Wnt/beta -Catenin Signaling during Embryogenesis in the Mouse. Mol. Cell. Biol. 18: 1248-1256 [Abstract] [Full Text]  
  • Ikeya, M, Takada, S (1998). Wnt signaling from the dorsal neural tube is required for the formation of the medial dermomyotome. Development 125: 4969-4976 [Abstract]  
  • Melkonyan, H. S., Chang, W. C., Shapiro, J. P., Mahadevappa, M., Fitzpatrick, P. A., Kiefer, M. C., Tomei, L. D., Umansky, S. R. (1997). SARPs: A family of secreted apoptosis-related proteins. Proc. Natl. Acad. Sci. USA 94: 13636-13641 [Abstract] [Full Text]  
  • Humphreys, R. C., Lydon, J., O’Malley, B. W., Rosen, J. M. (1997). Mammary Gland Development Is Mediated by Both Stromal and Epithelial Progesterone Receptors. Mol. Endocrinol. 11: 801-811 [Abstract] [Full Text]  
  • Eisenberg, C., Gourdie, R., Eisenberg, L. (1997). Wnt-11 is expressed in early avian mesoderm and required for the differentiation of the quail mesoderm cell line QCE-6. Development 124: 525-536 [Abstract]  
  • Munsterberg, A E, Kitajewski, J, Bumcrot, D A, McMahon, A P, Lassar, A B (1995). Combinatorial signaling by Sonic hedgehog and Wnt family members induces myogenic bHLH gene expression in the somite.. Genes Dev. 9: 2911-2922 [Abstract]  
  • Stern, H., Brown, A., Hauschka, S. (1995). Myogenesis in paraxial mesoderm: preferential induction by dorsal neural tube and by cells expressing Wnt-1. Development 121: 3675-3686 [Abstract]  
  • Kelly, G., Greenstein, P, Erezyilmaz, D., Moon, R. (1995). Zebrafish wnt8 and wnt8b share a common activity but are involved in distinct developmental pathways. Development 121: 1787-1799 [Abstract]  
  • Song, D. H., Sussman, D. J., Seldin, D. C. (2000). Endogenous Protein Kinase CK2 Participates in Wnt Signaling in Mammary Epithelial Cells. J. Biol. Chem. 275: 23790-23797 [Abstract] [Full Text]  
  • Lin, S.-Y., Xia, W., Wang, J. C., Kwong, K. Y., Spohn, B., Wen, Y., Pestell, R. G., Hung, M.-C. (2000). beta -Catenin, a novel prognostic marker for breast cancer: Its roles in cyclin D1 expression and cancer progression. Proc. Natl. Acad. Sci. USA 97: 4262-4266 [Abstract] [Full Text]  
  • You, Z., Saims, D., Chen, S., Zhang, Z., Guttridge, D. C., Guan, K.-l., MacDougald, O. A., Brown, A. M.C., Evan, G., Kitajewski, J., Wang, C.-Y. (2002). Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced apoptosis. JCB 157: 429-440 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»