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Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma Protuberans (DP)

Oncogene volume 20, pages 2965–2975 (2001)Cite this article

Abstract

Dermatofibrosarcoma protuberans (DP), an infiltrative skin tumour of intermediate malignancy, presents specific cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) or supernumerary ring chromosomes derived from t(17;22). We have previously shown that both rings and translocated chromosomes derived from t(17;22) presented the same molecular rearrangement with fusion of the COL1A1 gene on chromosome 17 to the PDGFB gene on chromosome 22. To study the structure and function of the COL1A1–PDGFB chimeric protein, we used a tumour-derived chimeric COL1A1–PDGFB cDNA to perform stable and transient transfections in the Chinese hamster lung fibroblastic cell line PS200 and the human epithelial cell line HEK293. We demonstrated that the stably transfected clones that expressed the COL1A1–PDGFB chimeric protein became growth factors independent and tumorigenic in nude mice. In addition, COL1A1–PDGFB transfected cell supernatants significantly stimulated fibroblastic cell growth, through the activation of the PDGFB receptor pathway. By using anti-PDGFB and specific anti-COL1A1–PDGFB antibodies, we showed that, similar to PDGFB, the COL1A1–PDGFB chimeric proteins are processed in transfected cells into mature PDGFB dimers. These results strongly suggest that the COL1A1–PDGFB chimeric gene expression associated with DP, induces tumours formation through production of mature PDGFB, in an autocrine or paracrine way. Strikingly, mutagenesis experiments indicated that uncleaved COL1A1–PDGFB forms are mitogenic and therefore could contribute, as well as mature PDGFB, to the establishment of a transformed phenotype.

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Acknowledgements

We thank Marie-Josée Terrier-Lacombe and Jean-Michel Coindre for providing samples of tumours, and we are grateful to Florence Pedeutour, Soumeya Bekri and Christiane Brahimi-Horn for the critical review of the manuscript and to Roselyne Tournaire for helpful discussions and suggestions. This study was supported in part by CNRS, the Association pour la Recherche sur le Cancer and the Ligue Nationale contre le Cancer.

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  1. Institute of Signalling, Developmental Biology and Cancer Research, CNRS UMR 6543, Centre Antoine-Lacassagne, Nice, 06189, Cedex 2, France

    Marie-Pierre Simon, Muriel Navarro, Danièle Roux & Jacques Pouysségur

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  1. Marie-Pierre Simon
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  3. Danièle Roux
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Simon, MP., Navarro, M., Roux, D. et al. Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma Protuberans (DP). Oncogene 20, 2965–2975 (2001). https://doi.org/10.1038/sj.onc.1204426

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