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

• Published in: Experimental cell research Vol. 241; no. 1; pp. 134 - 141
• Main Authors: Olson, D J, Gibo, D M
• Format: Journal Article
• Language: English
• 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
• DOI: 10.1006/excr.1998.4030
• ISSN: 0014-4827

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.