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 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.
Olson
D J
DJ
Department of Surgery, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey 17033, USA.
Gibo
D M
DM
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D016373:DNA, Antisense / Q000235:genetics*; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014170:Transformation, Genetic / Q000235:genetics; D014316:Tritium; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D016373:DNA, Antisense; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D014316:Tritium; D012313:RNA; D013936:Thymidine