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PMID: 8065359 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Differential transformation of mammary epithelial cells by Wnt genes.

Molecular and cellular biology ·Vol. 14 ·No. 9 ·1994-09-00 ·Pages 6278-86

Wong GT, Gavin BJ, McMahon AP

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.

Related Genes
Wnt-1 Wnt-1fs Wnt-2 Wnt-3A Wnt-4 Wnt-5A Wnt-5B Wnt-6 Wnt-7A Wnt-7B
MeSH Terms
Animals Cell Cycle Cell Line Cell Transformation, Neoplastic/genetics Culture Media Epithelial Cells Gene Expression Glycoproteins/physiology In Vitro Techniques Mammary Glands, Animal/cytology Mice Proto-Oncogene Proteins/genetics Proto-Oncogenes RNA, Messenger/genetics Transfection
Chemicals
Culture Media Glycoproteins Proto-Oncogene Proteins RNA, Messenger
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wong G T
Roche Institute of Molecular Biology, Nutley, New Jersey 07110.
Gavin B J
McMahon A P
References (52)
52 references, click to expand
  1. A retrovirus vector expressing the putative mammary oncogene int-1 causes partial transformation of a mammary epithelial cell line.
    Cell. 1986 Sep 26;46(7):1001-9 PMID: 3019559
  2. Hyperplasia of mouse mammary epithelium induced by expression of the Wnt-1 (int-1) oncogene in reconstituted mammary gland.
    Oncogene. 1992 Oct;7(10):2041-51 PMID: 1408145
  3. Transfection of the int-1 mammary oncogene in cuboidal RAC mammary cell line results in morphological transformation and tumorigenicity.
    EMBO J. 1987 Jan;6(1):127-31 PMID: 3034569
  4. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  5. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless.
    Cell. 1987 Aug 14;50(4):649-57 PMID: 3111720
  6. Local effects of EGF, alpha-TGF, and EGF-like growth factors on lobuloalveolar development of the mouse mammary gland in vivo.
    J Cell Physiol. 1987 Sep;132(3):581-4 PMID: 3498730
  7. Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless.
    EMBO J. 1988 Jun;7(6):1743-8 PMID: 2971536
  8. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice.
    Cell. 1988 Nov 18;55(4):619-25 PMID: 3180222
  9. Growth control and differentiation in mammary epithelial cells.
    Environ Health Perspect. 1989 Mar;80:85-99 PMID: 2647487
  10. The segment polarity phenotype of Drosophila involves differential tendencies toward transformation and cell death.
    Dev Biol. 1989 Jul;134(1):130-45 PMID: 2731645
  11. TGF-beta 1-induced inhibition of mouse mammary ductal growth: developmental specificity and characterization.
    Dev Biol. 1989 Sep;135(1):20-30 PMID: 2767334
  12. Demonstration of an adhering-junction molecule (plakoglobin) in the autoantigens of pemphigus foliaceus and pemphigus vulgaris.
    N Engl J Med. 1989 Sep 7;321(10):631-5 PMID: 2770792
  13. Ectopic expression of the proto-oncogene int-1 in Xenopus embryos leads to duplication of the embryonic axis.
    Cell. 1989 Sep 22;58(6):1075-84 PMID: 2673541
  14. Distribution of the wingless gene product in Drosophila embryos: a protein involved in cell-cell communication.
    Cell. 1989 Nov 17;59(4):739-49 PMID: 2582493
  15. Inhibition of mouse mammary ductal morphogenesis and down-regulation of the EGF receptor by epidermal growth factor.
    Dev Biol. 1990 Feb;137(2):425-33 PMID: 2303169
  16. The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix.
    EMBO J. 1990 May;9(5):1569-75 PMID: 2158444
  17. Secreted int-1 protein is associated with the cell surface.
    Mol Cell Biol. 1990 Jun;10(6):2723-30 PMID: 2140430
  18. Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast.
    Cell. 1990 Jun 15;61(6):1121-35 PMID: 1693546
  19. TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.
    Cell. 1990 Jun 15;61(6):1137-46 PMID: 2350785
  20. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice.
    Cell. 1990 Jun 15;61(6):1147-55 PMID: 2161707
  21. Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain.
    Proc Natl Acad Sci U S A. 1990 Jun;87(12):4519-23 PMID: 2162045
  22. Cadherins: a molecular family important in selective cell-cell adhesion.
    Annu Rev Biochem. 1990;59:237-52 PMID: 2197976
  23. Desmoglein shows extensive homology to the cadherin family of cell adhesion molecules.
    Biochem Biophys Res Commun. 1990 Dec 31;173(3):1224-30 PMID: 1702628
  24. Expression of multiple novel Wnt-1/int-1-related genes during fetal and adult mouse development.
    Genes Dev. 1990 Dec;4(12B):2319-32 PMID: 2279700
  25. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice.
    Cell. 1991 Feb 22;64(4):693-702 PMID: 1997203
  26. Identification of desmoglein, a constitutive desmosomal glycoprotein, as a member of the cadherin family of cell adhesion molecules.
    Eur J Cell Biol. 1990 Oct;53(1):1-12 PMID: 1706270
  27. Injected Wnt RNA induces a complete body axis in Xenopus embryos.
    Cell. 1991 Nov 15;67(4):741-52 PMID: 1834344
  28. Analysis of Xwnt-4 in embryos of Xenopus laevis: a Wnt family member expressed in the brain and floor plate.
    Development. 1992 Jun;115(2):463-73 PMID: 1425335
  29. p120, a novel substrate of protein tyrosine kinase receptors and of p60v-src, is related to cadherin-binding factors beta-catenin, plakoglobin and armadillo.
    Oncogene. 1992 Dec;7(12):2439-45 PMID: 1334250
  30. Overlapping expression of Xwnt-3A and Xwnt-1 in neural tissue of Xenopus laevis embryos.
    Dev Biol. 1993 Jan;155(1):46-57 PMID: 8416844
  31. Localization and quantification of Wnt-2 gene expression in mouse mammary development.
    Dev Biol. 1993 Jan;155(1):87-96 PMID: 8416847
  32. Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis.
    Development. 1993 Sep;119(1):97-111 PMID: 8275867
  33. Changes in insulin responsiveness during development of mammary epithelium.
    J Cell Biol. 1974 Aug;62(2):550-6 PMID: 4426918
  34. The development of wingless, a homeotic mutation of Drosophila.
    Dev Biol. 1977 APR;56(2):227-40 PMID: 849798
  35. 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 PMID: 213889
  36. Epidermal growth factor requirement for development of cultured mammary gland.
    Nature. 1980 May 22;285(5762):250-2 PMID: 6966378
  37. Mutations affecting segment number and polarity in Drosophila.
    Nature. 1980 Oct 30;287(5785):795-801 PMID: 6776413
  38. Insulin is essential for accumulation of casein mRNA in mouse mammary epithelial cells.
    Proc Natl Acad Sci U S A. 1981 Sep;78(9):5682-4 PMID: 7029543
  39. Changes in Scatchard plots for insulin binding to mammary epithelial cells from cycling, pregnant, and lactating mice.
    Endocrinology. 1982 Jan;110(1):176-82 PMID: 7032894
  40. 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 PMID: 6297757
  41. Epidermal growth factor stimulates cell proliferation and inhibits functional differentiation of mouse mammary epithelial cells in culture.
    Endocrinology. 1983 Sep;113(3):871-7 PMID: 6603352
  42. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.
    Nature. 1984 Jan 12-18;307(5947):131-6 PMID: 6318122
  43. Structure and nucleotide sequence of the putative mammary oncogene int-1; proviral insertions leave the protein-encoding domain intact.
    Cell. 1984 Nov;39(1):233-40 PMID: 6091914
  44. Injected Xwnt-8 RNA acts early in Xenopus embryos to promote formation of a vegetal dorsalizing center.
    Cell. 1991 Nov 15;67(4):753-65 PMID: 1657405
  45. Secretion and movement of wingless protein in the epidermis of the Drosophila embryo.
    Mech Dev. 1991 Aug;35(1):43-54 PMID: 1720017
  46. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin.
    Science. 1991 Nov 29;254(5036):1359-61 PMID: 1962194
  47. The mouse Wnt-1 gene can act via a paracrine mechanism in transformation of mammary epithelial cells.
    Mol Cell Biol. 1992 Jan;12(1):321-8 PMID: 1530877
  48. The biochemical properties and transforming potential of human Wnt-2 are similar to Wnt-1.
    Oncogene. 1992 Jan;7(1):153-61 PMID: 1371336
  49. Differential regulation of the Wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland.
    Mol Cell Biol. 1992 May;12(5):2418-23 PMID: 1373817
  50. Mutational analysis of mouse Wnt-1 identifies two temperature-sensitive alleles and attributes of Wnt-1 protein essential for transformation of a mammary cell line.
    Mol Biol Cell. 1992 May;3(5):521-33 PMID: 1535241
  51. Wnt genes.
    Cell. 1992 Jun 26;69(7):1073-87 PMID: 1617723
  52. Autonomous requirements for the segment polarity gene armadillo during Drosophila embryogenesis.
    Cell. 1987 Apr 24;49(2):177-84 PMID: 3105892
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.9.6278-6286.1994
Published
1994-09-00
Pages
6278-86
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359154
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.9.6278-6286.1994 PMC Full Text View journal details
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