Expression of a down-regulated target, SSeCKS, reverses v-Jun-induced transformation of 10T1/2 murine fibroblasts.
Line 10T1/2 mouse fibroblast overexpressing the v-Jun oncoprotein were morphologically altered, grew into multilayered foci in culture and formed colonies when suspended in agar. The growth rate of the v-Jun-transformed 10T1/2 cells was not changed significantly from that of the untransformed parental cells, but the saturation density of the transformed cultures exceeded that of normal controls by a factor of 2. mRNA extracted from v-Jun-transformed 10T1/2 cells was analysed for differential gene expression with DNA micro-array technology. One of the targets downregulated by v-Jun was identified as SSeCKS (Src-suppressed C kinase substrate). Re-expression of SSeCKS in v-Jun-transformed fibroblasts reversed the transformed phenotype of the cells. Their ability to form foci was reduced to background levels, the number and size of agar colonies was lowered by a factor of 10 and the saturation density was significantly diminished. However, expression of SSeCKS had little effect on the morphology of v-Jun-transformed 10T1/2 cells. These data suggest that the SSeCKS protein has growth-attenuating properties. Down-regulation of SSeCKS may be essential for Jun-induced transformation.
Cohen
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Gen-Probe Incorporated, 10210 Genetic Center Drive, San Diego, California CA 92121, USA.
Waha
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Gelman
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Vogt
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D054758:A Kinase Anchor Proteins; D000818:Animals; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008934:Mitogens / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D014410:Tumor Stem Cell Assay
D054758:A Kinase Anchor Proteins; C491161:Akap12 protein, mouse; D018797:Cell Cycle Proteins; D008934:Mitogens; D016759:Oncogene Protein p65(gag-jun)