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

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 ec...

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Bibliographic Details
Published inExperimental cell research Vol. 241; no. 1; pp. 134 - 141
Main Authors Olson, D J, Gibo, D M
Format Journal Article
LanguageEnglish
Published United States 25.05.1998
Subjects
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
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Summary: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.
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ISSN:0014-4827
DOI:10.1006/excr.1998.4030