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Transformation and Morphological Changes of Murine L Cells by Transfection with a Mutated Form of ß-Catenin¹

Division of Clinical Genetics, Department of Medical Genetics, Biomedical Research Center, Osaka University Medical School [Y. Nag., Y. Mi., K. I., Y. Nak.], and Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University [Y. Nag., Y. S., Y. Ma.], Osaka 565-0871; and Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639 [Y. Nak.], Japan

To shed light on the oncogenic nature of mutant ß-catenin, we introduced a form of the cDNA that lacked an entire exon 3 into L cells derived from murine s.c. tissue. Aberrant ß-catenin protein accumulated in the cytoplasm and nuclei of these cells (designated L-MT), whereas in L cells transfected with wild-type ß-catenin (designated L-N), normal ß-catenin protein was expressed at a level similar to that of parental cells. L-MT cells also changed morphologically from a fibroblast-like appearance to a more cuboidal shape. Their rate of proliferation was the same as that of L cells and L-N cells, but the saturation density of L-MT cells appeared to increase in association with a multilayer growth pattern. Furthermore, L-MT cells required a lower concentration of serum in the growth medium than did parental cells. These alterations in cell growth and morphology suggested that mutated ß-catenin was stabilized in the transfected cells and induced the oncogenic phenotype.

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