| Autor: |
Nijman SMB; Division of Molecular Carcinogenesis and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands., Hijmans EM; Division of Molecular Carcinogenesis and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands., Messaoudi SE; Institut de Genetique Moleculaire, Unité Mixte de Recherche 5535/IFR24 CNRS, 1919 Route de Mende 34293, Montpellier Cedex 5, France., van Dongen MMW; Division of Molecular Carcinogenesis and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands., Sardet C; Institut de Genetique Moleculaire, Unité Mixte de Recherche 5535/IFR24 CNRS, 1919 Route de Mende 34293, Montpellier Cedex 5, France., Bernards R; Division of Molecular Carcinogenesis and Centre for Biomedical Genetics, The Netherlands Cancer Institute, 121 Plesmanlaan, 1066 CX Amsterdam, The Netherlands. Electronic address: r.bernards@nki.nl. |
| Abstrakt: |
The helix-loop-helix transcription factor TFE3 has been suggested to play a role in the control of cell growth by acting as a binding partner of transcriptional regulators such as E2F3, SMAD3, and LEF-1. Furthermore, translocations/TFE3 fusions have been directly implicated in tumorigenesis. Surprisingly, however, a direct functional role for TFE3 in the regulation of proliferation has not been reported. By screening retroviral cDNA expression libraries to identify cDNAs that confer resistance to a pRB-induced proliferation arrest, we have found that TFE3 overrides a growth arrest in Rat1 cells induced by pRB and its upstream regulator p16(INK4A). In addition, TFE3 expression blocks the anti-mitogenic effects of TGF-beta in rodent and human cells. We provide data supporting a role for endogenous TFE3 in the direct regulation of CYCLIN E expression in an E2F3-dependent manner. These observations establish TFE3 as a functional regulator of proliferation and offer a potential mechanism for its involvement in cancer. |
