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Cell Growth & Differentiation, Vol 8, Issue 12 1349-1358, Copyright © 1997 by American Association of Cancer Research

ARTICLES

Transformation by Wnt family proteins correlates with regulation of beta-catenin

H Shimizu, MA Julius, M Giarre, Z Zheng, AM Brown and J Kitajewski
Strang-Cornell Cancer Research Laboratory, Cornell University Medical College, New York, New York 10021, USA.

Several members of the Wnt family of secreted factors are strongly implicated as regulators of mammary cell growth and differentiation. To investigate Wnt signaling in mammary cells, we have assessed the abilities of 10 different Wnt genes to cause transformation of C57MG mammary epithelial cells and in parallel studied their effects on beta-catenin, a component of the Wnt-1 signaling pathway. Autocrine transforming potential was tested by expression of Wnt proteins in C57MG cells, and paracrine effects were evaluated by coculture of C57MG cells with fibroblasts secreting different Wnt proteins. Western blotting confirmed the expression of each Wnt protein in the relevant cell lines. Activities of the 10 Wnts tested were divisible into three groups. Wnt-1, Wnt-2, Wnt-3, and Wnt3a induced strong transformation and an elongated refractile cell morphology. Wnt-6 and Wnt-7a produced weak morphological changes. Wnt-4, Wnt-5a, Wnt-5b, and Wnt-7b had no effect at all on C57MG morphology. Analysis of beta-catenin levels showed that the transforming Wnts induced accumulation of cytosolic beta-catenin, whereas nontransforming Wnts did not. These result demonstrate that several Wnt family members are capable of elevating beta-catenin levels and suggest that their signaling pathways share intracellular signaling components. The correlation between increased cytosolic beta-catenin levels and C57MG transformation supports a role for beta-catenin in transformation of these cells. These data also imply the existence of receptors that respond to certain Wnt proteins but not to others.


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J. Cell Biol., April 29, 2002; 157(3): 429 - 440.
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M. W. Briggs, Z. Li, and D. B. Sacks
IQGAP1-mediated Stimulation of Transcriptional Co-activation by {beta}-Catenin Is Modulated by Calmodulin
J. Biol. Chem., March 1, 2002; 277(9): 7453 - 7465.
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 DevelopmentHome page
J.-H. Ryu, S.-J. Kim, S.-H. Kim, C.-D. Oh, S.-G. Hwang, C.-H. Chun, S.-H. Oh, J.-K. Seong, T.-L. Huh, and J.-S. Chun
Regulation of the chondrocyte phenotype by {beta}-catenin
Development, January 12, 2002; 129(23): 5541 - 5550.
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W. Hsu, R. Shakya, and F. Costantini
Impaired mammary gland and lymphoid development caused by inducible expression of Axin in transgenic mice
J. Cell Biol., December 10, 2001; 155(6): 1055 - 1064.
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 ScienceHome page
G. K. Dhoot, M. K. Gustafsson, X. Ai, W. Sun, D. M. Standiford, and C. P. Emerson Jr.
Regulation of Wnt Signaling and Embryo Patterning by an Extracellular Sulfatase
Science, August 31, 2001; 293(5535): 1663 - 1666.
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 DevelopmentHome page
I. Skromne and C. D. Stern
Interactions between Wnt and Vg1 signalling pathways initiate primitive streak formation in the chick embryo
Development, August 1, 2001; 128(15): 2915 - 2927.
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 Proc. Natl. Acad. Sci. USAHome page
J. Galceran, S.-C. Hsu, and R. Grosschedl
Rescue of a Wnt mutation by an activated form of LEF-1: Regulation of maintenance but not initiation of Brachyury expression
PNAS, July 17, 2001; 98(15): 8668 - 8673.
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T. Yamane, T. Kunisada, H. Tsukamoto, H. Yamazaki, H. Niwa, S. Takada, and S.-I. Hayashi
Wnt Signaling Regulates Hemopoiesis Through Stromal Cells
J. Immunol., July 15, 2001; 167(2): 765 - 772.
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 J Biol ChemHome page
H. C. Mertani, T. Zhu, E. L. K. Goh, K.-O. Lee, G. Morel, and P. E. Lobie
Autocrine Human Growth Hormone (hGH) Regulation of Human Mammary Carcinoma Cell Gene Expression: IDENTIFICATION OF CHOP AS A MEDIATOR OF hGH-STIMULATED HUMAN MAMMARY CARCINOMA CELL SURVIVAL
J. Biol. Chem., June 15, 2001; 276(24): 21464 - 21475.
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M. Jonsson and T. Andersson
Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells
J. Cell Sci., June 1, 2001; 114(11): 2043 - 2053.
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 Cancer Res.Home page
W. Szeto, W. Jiang, D. A. Tice, B. Rubinfeld, P. G. Hollingshead, S. E. Fong, D. L. Dugger, T. Pham, D. G. Yansura, T. A. Wong, et al.
Overexpression of the Retinoic Acid-responsive Gene Stra6 in Human Cancers and Its Synergistic Induction by Wnt-1 and Retinoic Acid
Cancer Res., May 1, 2001; 61(10): 4197 - 4205.
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 JCBHome page
A. Imbert, R. Eelkema, S. Jordan, H. Feiner, and P. Cowin
{Delta}n89{beta}-Catenin Induces Precocious Development, Differentiation, and Neoplasia in Mammary Gland
J. Cell Biol., April 30, 2001; 153(3): 555 - 568.
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 Mol. Cell. Biol.Home page
S. Goruppi, C. Chiaruttini, M. E. Ruaro, B. Varnum, and C. Schneider
Gas6 Induces Growth, {beta}-Catenin Stabilization, and T-Cell Factor Transcriptional Activation in Contact-Inhibited C57 Mammary Cells
Mol. Cell. Biol., February 1, 2001; 21(3): 902 - 915.
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 JCBHome page
S. Chen, D. C. Guttridge, Z. You, Z. Zhang, A. Fribley, M. W. Mayo, J. Kitajewski, and C.-Y. Wang
WNT-1 Signaling Inhibits Apoptosis by Activating {beta}-Catenin/T Cell Factor-Mediated Transcription
J. Cell Biol., January 8, 2001; 152(1): 87 - 96.
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 Proc. Natl. Acad. Sci. USAHome page
R. Calvo, J. West, W. Franklin, P. Erickson, L. Bemis, E. Li, B. Helfrich, P. Bunn, J. Roche, E. Brambilla, et al.
Altered HOX and WNT7A expression in human lung cancer
PNAS, November 7, 2000; 97(23): 12776 - 12781.
[Abstract] [Full Text] [PDF]

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 J Biol ChemHome page
M. Haertel-Wiesmann, Y. Liang, W. J. Fantl, and L. T. Williams
Regulation of Cyclooxygenase-2 and Periostin by Wnt-3 in Mouse Mammary Epithelial Cells
J. Biol. Chem., October 13, 2000; 275(41): 32046 - 32051.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
K. J. Dunn, B. O. Williams, Y. Li, and W. J. Pavan
Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development
PNAS, August 29, 2000; 97(18): 10050 - 10055.
[Abstract] [Full Text] [PDF]

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D. H. Song, D. J. Sussman, and D. C. Seldin
Endogenous Protein Kinase CK2 Participates in Wnt Signaling in Mammary Epithelial Cells
J. Biol. Chem., August 4, 2000; 275(31): 23790 - 23797.
[Abstract] [Full Text] [PDF]

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P. Polakis
Wnt signaling and cancer
Genes & Dev., August 1, 2000; 14(15): 1837 - 1851.
[Full Text]

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 JCBHome page
T. Toyofuku, Z. Hong, T. Kuzuya, M. Tada, and M. Hori
WNT/Frizzled-2 Signaling Induces Aggregation and Adhesion among Cardiac Myocytes by Increased Cadherin-{beta}-Catenin Complex
J. Cell Biol., July 10, 2000; 150(1): 225 - 242.
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S. Naylor, M. J. Smalley, D. Robertson, B. A. Gusterson, P. A. Edwards, and T. C. Dale
Retroviral expression of Wnt-1 and Wnt-7b produces different effects in mouse mammary epithelium
J. Cell Sci., June 15, 2000; 113(12): 2129 - 2138.
[Abstract] [PDF]

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 J Biol ChemHome page
R.-H. Chen, W. V. Ding, and F. McCormick
Wnt Signaling to {beta}-Catenin Involves Two Interactive Components: GLYCOGEN SYNTHASE KINASE-3{beta} INHIBITION AND ACTIVATION OF PROTEIN KINASE C
J. Biol. Chem., June 9, 2000; 275(23): 17894 - 17899.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
S Allard, P Adin, L Gouedard, N di Clemente, N Josso, M. Orgebin-Crist, J. Picard, and F Xavier
Molecular mechanisms of hormone-mediated Mullerian duct regression: involvement of beta-catenin
Development, January 8, 2000; 127(15): 3349 - 3360.
[Abstract] [PDF]

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 DevelopmentHome page
C Hartmann and C. Tabin
Dual roles of Wnt signaling during chondrogenesis in the chicken limb
Development, January 7, 2000; 127(14): 3141 - 3159.
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 J. Cell Sci.Home page
S. Dennis, M. Aikawa, W. Szeto, P. A. d'Amore, and J. Papkoff
A secreted frizzled related protein, FrzA, selectively associates with Wnt-1 protein and regulates wnt-1 signaling
J. Cell Sci., November 1, 1999; 112(21): 3815 - 3820.
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 Mol. Biol. CellHome page
M. W. Klymkowsky, B. O. Williams, G. D. Barish, H. E. Varmus, and Y. E. Vourgourakis
Membrane-anchored Plakoglobins Have Multiple Mechanisms of Action in Wnt Signaling
Mol. Biol. Cell, October 1, 1999; 10(10): 3151 - 3169.
[Abstract] [Full Text]

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 Cancer Res.Home page
Y. Nagasawa, Y. Miyoshi, K. Iwao, Y. Shinomura, Y. Matsuzawa, and Y. Nakamura
Transformation and Morphological Changes of Murine L Cells by Transfection with a Mutated Form of {beta}-Catenin
Cancer Res., August 1, 1999; 59(15): 3539 - 3542.
[Abstract] [Full Text] [PDF]

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 J Biol ChemHome page
J.-S. Lee, A. Ishimoto, and S.-i. Yanagawa
Characterization of Mouse Dishevelled (Dvl) Proteins in Wnt/Wingless Signaling Pathway
J. Biol. Chem., July 23, 1999; 274(30): 21464 - 21470.
[Abstract] [Full Text] [PDF]

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 J Biol ChemHome page
H. Yamamoto, S. Kishida, M. Kishida, S. Ikeda, S. Takada, and A. Kikuchi
Phosphorylation of Axin, a Wnt Signal Negative Regulator, by Glycogen Synthase Kinase-3{beta} Regulates Its Stability
J. Biol. Chem., April 16, 1999; 274(16): 10681 - 10684.
[Abstract] [Full Text] [PDF]

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 J Biol ChemHome page
W. Hsu, L. Zeng, and F. Costantini
Identification of a Domain of Axin That Binds to the Serine/Threonine Protein Phosphatase 2A and a Self-binding Domain
J. Biol. Chem., February 5, 1999; 274(6): 3439 - 3445.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
D. Pennica, T. A. Swanson, J. W. Welsh, M. A. Roy, D. A. Lawrence, J. Lee, J. Brush, L. A. Taneyhill, B. Deuel, M. Lew, et al.
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
PNAS, December 8, 1998; 95(25): 14717 - 14722.
[Abstract] [Full Text] [PDF]

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 Mol. Cell. Biol.Home page
C. S. Young, M. Kitamura, S. Hardy, and J. Kitajewski
Wnt-1 Induces Growth, Cytosolic {beta}-Catenin, and Tcf/Lef Transcriptional Activation in Rat-1 Fibroblasts
Mol. Cell. Biol., May 1, 1998; 18(5): 2474 - 2485.
[Abstract] [Full Text] [PDF]

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 J Biol ChemHome page
M. Haertel-Wiesmann, Y. Liang, W. J. Fantl, and L. T. Williams
Regulation of Cyclooxygenase-2 and Periostin by Wnt-3 in Mouse Mammary Epithelial Cells
J. Biol. Chem., October 13, 2000; 275(41): 32046 - 32051.
[Abstract] [Full Text] [PDF]

Home page
 J Biol ChemHome page
H. C. Mertani, T. Zhu, E. L. K. Goh, K.-O. Lee, G. Morel, and P. E. Lobie
Autocrine Human Growth Hormone (hGH) Regulation of Human Mammary Carcinoma Cell Gene Expression: IDENTIFICATION OF CHOP AS A MEDIATOR OF hGH-STIMULATED HUMAN MAMMARY CARCINOMA CELL SURVIVAL
J. Biol. Chem., June 15, 2001; 276(24): 21464 - 21475.
[Abstract] [Full Text] [PDF]

Home page
 J Biol ChemHome page
R.-H. Chen, W. V. Ding, and F. McCormick
Wnt Signaling to {beta}-Catenin Involves Two Interactive Components: GLYCOGEN SYNTHASE KINASE-3{beta} INHIBITION AND ACTIVATION OF PROTEIN KINASE C
J. Biol. Chem., June 9, 2000; 275(23): 17894 - 17899.
[Abstract] [Full Text] [PDF]


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