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Transformation capacities of the papillary renal cell carcinoma-associated PRCCTFE3 and TFE3PRCC fusion genes

Oncogene volume 20, pages 1414–1424 (2001)Cite this article

Abstract

A recurrent chromosomal abnormality associated with a subset of papillary renal cell carcinomas is t(X;1)(p11;q21). This translocation leads to the formation of two fusion genes, TFE3PRCC and the reciprocal product PRCCTFE3. Both fusion genes are expressed in t(X;1)-positive renal cell carcinomas and contain major parts of the coding regions of the parental transcription factor PRCC and TFE3 genes, respectively. To find out whether these fusion genes possess transforming capacity, we transfected NIH3T3 and rat-1 cells with the fusion products, either separately or combined. When using soft agar assays, we observed colony formation in all cases. NIH3T3 cells transfected with PRCCTFE3 or PRCCTFE3 together with TFE3PRCC yielded the highest colony forming capacities. Examination of other characteristics associated with malignant transformation, i.e., growth under low-serum conditions and formation of tumors in athymic nude mice, revealed that cells transfected with PRCCTFE3 exhibited all these transformation-associated characteristics. Upon transfection of the fusion products into conditionally immortalized kidney cells, derived from the proximal tubules of an H-2Kb-tsA58 transgenic mouse, and consecutive incubation under non-permissive conditions, growth arrest was observed, followed by differentiation except for those cells transfected with PRCCTFE3. Therefore, we conclude that PRCCTFE3 may be the t(X;1)-associated fusion product that is most critical for the development of papillary renal cell carcinomas.

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Acknowledgements

This work was supported by the Dutch Cancer Society, grant 98-1804. We thank Dr R Bindels (Dept. Cell Physiology), Ad de Groof and Frank Oerlemans (Dept. Cell Biology) for their advice regarding the establishment of the conditionally immortalized cell lines. Stef Mentzel and Dr KJM Assmann (Dept. Pathology) are gratefully acknowledged for providing the aminopeptidase A and dipeptidyl peptidase IV specific primers. Liesbeth Pierson (Dept. General Instrumentation) is acknowledged for capturing the images of the conditionally immortalized cell lines.

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  1. Marian A J Weterman

    Present address: Department of Pathology, Academic Medical Center Amsterdam, The Netherlands

  2. Anita den Hartog

    Present address: Department of Cell Physiology, University Medical Center Nijmegen, The Netherlands

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  1. Department of Human Genetics, University Medical Center Nijmegen, The Netherlands

    Marian A J Weterman, Jan J M van Groningen & Ad Geurts van Kessel

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  1. Marian A J Weterman
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Weterman, M., van Groningen, J., den Hartog, A. et al. Transformation capacities of the papillary renal cell carcinoma-associated PRCCTFE3 and TFE3PRCC fusion genes. Oncogene 20, 1414–1424 (2001). https://doi.org/10.1038/sj.onc.1204213

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