Antisense wnt-5a mimics wnt-1-mediated C57MG mammary epithelial cell transformation

Exp Cell Res. 1998 May 25;241(1):134-41. doi: 10.1006/excr.1998.4030.

Abstract

The disruption of the normal expression of wnt-5a in cell lines and in tumors is becoming increasingly recognized as important in cell transformation and tumorigenesis. For example, in endometrial cancer wnt-5a is downregulated compared to normal tissue. Our laboratory has recently found that the ectopic expression of wnt-5a in human RCC23 renal carcinoma cells missing wnt-5a gene expression suppresses in vitro cell growth and telomerase enzyme activity. Furthermore, ectopic wnt-5a in MC-T16 uroepithelial cancer cells missing the region of chromosome 3p where wnt-5a has been mapped reverts uroepithelial cell tumorigenesis in athymic nude mice. These studies were based upon the previous finding that wnt-1 and wnt-2 transform C57MG mammary epithelial cells by downregulating the endogenous expression of wnt-5a. We now report that transfecting C57MG cells with a mammalian expression vector carrying antisense wnt-5a results in a cell phenotype that mimics cell transformation by ectopic wnt-1 or wnt-2. Correspondingly, wnt-1-transformed cells are partially reverted in the presence of ectopic wnt-5a. We conclude from this that wnt-5a is an important regulator of cell growth and differentiation and its loss of expression leads to cell transformation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / genetics
  • Cell Division / physiology
  • Cell Line
  • DNA, Antisense / genetics*
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression / genetics
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism
  • Mice
  • Proto-Oncogene Proteins / genetics*
  • RNA / genetics
  • Thymidine / metabolism
  • Transformation, Genetic / genetics
  • Tritium
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt1 Protein
  • Zebrafish Proteins*

Substances

  • DNA, Antisense
  • Proto-Oncogene Proteins
  • WNT5A protein, human
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Zebrafish Proteins
  • Tritium
  • RNA
  • Thymidine