The ability of Fos family members to produce phenotypic changes in epithelioid cells is not directly linked to their transactivation potentials.
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.
Andersen
Henriette
H
Danish Cancer Society, Department of Molecular Cancer Biology, Strandboulevarden 49, DK-2100, Copenhagen Ø, Denmark.
Mahmood
Shaukat
S
Tkach
Vadim
V
Cohn
Martin
M
Kustikova
Olga
O
Grigorian
Mariam
M
Berezin
Vladimir
V
Bock
Elisabeth
E
Lukanidin
Eugene
E
Tulchinsky
Eugene
E
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D002460:Cell Line; D048429:Cell Size; D004268:DNA-Binding Proteins / Q000502:physiology*; D015622:Epithelioid Cells / Q000378:metabolism; D051921:Fos-Related Antigen-2; D051379:Mice; D010641:Phenotype; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000099169:Fos-Related Antigen 1
D004268:DNA-Binding Proteins; D051921:Fos-Related Antigen-2; D016760:Proto-Oncogene Proteins c-fos; D015534:Trans-Activators; D014157:Transcription Factors; D000099169:Fos-Related Antigen 1; C497873:Fosl2 protein, mouse