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Oncogene. 2002 Jul 18;21(31):4843-8.

The ability of Fos family members to produce phenotypic changes in epithelioid cells is not directly linked to their transactivation potentials.

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Danish Cancer Society, Department of Molecular Cancer Biology, Strandboulevarden 49, DK-2100, Copenhagen Ø, Denmark.


Numerous studies have revealed distinct functions of Fos proteins in different mouse tissues and cell lines. Here, we perform a direct comparison of the features of exogenous c-Fos, Fra-1 and Fra-2 proteins expressed in murine tumor cells of epithelial origin, CSML0. Although transactivation potential of c-Fos is much stronger than that of Fra-1 and Fra-2, all three proteins are capable of modulating transcription of target genes. Moreover, there is a certain degree of specificity in the induction of the transcription of AP-1-responsive genes by different Fos proteins. For instance, c-Fos and Fra-1 but not Fra-2 activated genes of the urokinase system. Additionally, not only a strong transcriptional activator c-Fos, but also Fra-1 induced morphological alterations in CSML0 cells. N-terminal domain of Fra-1 was required for this function. On the other hand, Fra-2 failed to change morphology of CSML0 cells. We therefore conclude that c-Fos, Fra-1 and Fra-2 differently activate transcription of target genes and induce morphological changes in epithelioid carcinoma cells in a manner not directly linked to their transactivation potentials.

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