Transformation by Wnt family proteins correlates with regulation of beta-catenin.
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.
Shimizu
H
H
Strang-Cornell Cancer Research Laboratory, Cornell University Medical College, New York, New York 10021, USA.
Julius
M A
MA
Giarré
M
M
Zheng
Z
Z
Brown
A M
AM
Kitajewski
J
J
D000818:Animals; D019898:Autocrine Communication; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006023:Glycoproteins; D015151:Immunoblotting; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D019899:Paracrine Communication; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators; D014162:Transfection; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D060528:Wnt4 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; C555507:WNT3 protein, human; C555510:WNT3A protein, human; C555581:WNT4 protein, human; C085389:WNT5A protein, human; C490674:WNT6 protein, human; C490675:WNT7B protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051154:Wnt2 Protein; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; C095936:Wnt6 protein, mouse; C490508:Wnt7a protein, mouse; C095937:Wnt7b protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin