RGD Reference Report - Transformation by Wnt family proteins correlates with regulation of beta-catenin. - Rat Genome Database

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

Authors: Shimizu, H  Julius, MA  Giarre, M  Zheng, Z  Brown, AM  Kitajewski, J 
Citation: Shimizu H, etal., Cell Growth Differ. 1997 Dec;8(12):1349-58.
RGD ID: 2298848
Pubmed: PMID:9419423   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Mammary Neoplasms  ISOWnt1 (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  IDA 2298848; 2298848; 2298848; 2298848; 2298848; 2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  ISOWnt3a (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms no_associationISOWnt5b (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  ISOWnt6 (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  ISOWnt7a (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms no_associationISOWnt7b (Mus musculus)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  ISOWNT2 (Homo sapiens)2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms  ISOWNT3 (Homo sapiens) and Wnt3 (Mus musculus)2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 
Experimental Mammary Neoplasms no_associationIDA 2298848; 2298848in vitro transformation of transfected C57MG mammary epithelial cell lineRGD 

Objects Annotated

Genes (Rattus norvegicus)
Wnt1  (Wnt family member 1)
Wnt2  (Wnt family member 2)
Wnt3  (Wnt family member 3)
Wnt3a  (Wnt family member 3A)
Wnt5b  (Wnt family member 5B)
Wnt6  (Wnt family member 6)
Wnt7a  (Wnt family member 7A)
Wnt7b  (Wnt family member 7B)

Genes (Mus musculus)
Wnt1  (wingless-type MMTV integration site family, member 1)
Wnt2  (wingless-type MMTV integration site family, member 2)
Wnt3  (wingless-type MMTV integration site family, member 3)
Wnt3a  (wingless-type MMTV integration site family, member 3A)
Wnt5b  (wingless-type MMTV integration site family, member 5B)
Wnt6  (wingless-type MMTV integration site family, member 6)
Wnt7a  (wingless-type MMTV integration site family, member 7A)
Wnt7b  (wingless-type MMTV integration site family, member 7B)

Genes (Homo sapiens)
WNT1  (Wnt family member 1)
WNT2  (Wnt family member 2)
WNT3  (Wnt family member 3)
WNT3A  (Wnt family member 3A)
WNT5B  (Wnt family member 5B)
WNT6  (Wnt family member 6)
WNT7A  (Wnt family member 7A)
WNT7B  (Wnt family member 7B)


Additional Information