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Cell context reveals a dual role for Maf in oncogenesis
- Source :
- Oncogene. 25(9)
- Publication Year :
- 2005
-
Abstract
- Maf b-Zip transcription factors are involved in both terminal differentiation and oncogenesis. To investigate this apparent contradiction, we used two different primary cell types and performed an extensive analysis of transformation parameters induced by Maf proteins. We show that MafA and c-Maf are potent oncogenes in chicken embryo fibroblasts, while MafB appears weaker. We also provide the first evidence that MafA can confer growth factor independence and promote cell division at low density. Moreover, using MafA as a model, we identified several parameters that are critical for Maf transforming activities. Indeed, MafA ability to induce anchorage-independent cell growth was sensitive to culture conditions. In addition, the transforming activity of MafA was dependent on its phosphorylation state, since mutation on Ser65 impaired its ability to induce growth at low density and anchorage-independent growth. We next examined transforming activity of large Maf proteins in embryonic neuroretina cells, where they are known to induce differentiation. Unlike v-Jun, MafA, MafB and c-Maf did not show oncogenic activity in these cells. Moreover, they counteracted transformation induced by constitutive activation of the Ras/Raf/MEK pathway. Taken together, our results show that Maf proteins could display antagonistic functions in oncogenesis depending on the cellular context, and support a dual role for Maf as both oncogenes and tumor suppressor-like proteins.
- Subjects :
- Cancer Research
Maf Transcription Factors, Large
Cell division
medicine.medical_treatment
Cell Culture Techniques
Context (language use)
Chick Embryo
Biology
medicine.disease_cause
Retina
Maf Transcription Factors
Genetics
medicine
Animals
Humans
Genes, Tumor Suppressor
Phosphorylation
Molecular Biology
Transcription factor
Cell Proliferation
Cell growth
Reverse Transcriptase Polymerase Chain Reaction
Growth factor
Oncogenes
Fibroblasts
Cell biology
Cell Transformation, Neoplastic
MAFB
Proto-Oncogene Proteins c-maf
Carcinogenesis
Cell Division
Plasmids
Subjects
Details
- ISSN :
- 09509232
- Volume :
- 25
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....775e0e0b43e9285d05e4b0f8baedc1ac