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A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts

Oncogene volume 26, pages 725–732 (2007)Cite this article

Abstract

In addition to its role in invasion and metastasis of several tumors, the multifunctional urokinase receptor uPAR (urokinase plasminogen activator receptor) is directly involved in the growth of several cancer cells in vitro and in vivo. We have compared growth rate and oncogenic transformation in wild-type (wt) or uPAR−/− mouse embryonic fibroblasts (MEFs). Surprisingly, uPAR−/− MEFs grew faster than wt MEFs. This agreed with elevated levels of cell cycle mediators like extracellular signal-regulated protein kinase, p38, AP1 and Cyclin D1. Infection with a uPAR retrovirus reverted the effect, decreasing the growth rate.When MEFs were transformed with H-RasV12 and E1A oncogenes, the efficiency of transformation in uPAR−/− MEFs was higher than in wt. UPAR−/− MEFs grew faster at low serum, produced more colonies in agar and produced tumors in vivo in nude mice with a lower latency period. The properties of the heterozygous uPAR+/− MEFs were always intermediate. We conclude therefore that in MEFs uPAR concentration controls cell proliferation and the transforming activity of some oncogenes.

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Acknowledgements

We are indebted to Davide Moi, Drs M van Lohuizen, Kristian Helin, Gunilla Hoyer-Hansen, Orla Cunningham and Cristina Moroni for useful discussions and the gift reagents. This work was supported by grants from AICR (Association for International Cancer Research, UK), AIRC (Italian Association for Cancer Research regional Grant), EU (IP Cancerdegradome EU CT 2003-503297; NoE MAIN, CT 2003-502935) and the Cariplo Foundation.

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  1. R Mazzieri and F Furlan: These authors have contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Biology and Functional Genomics, Università Vita Salute San Raffaele, Milano, Italy

    R Mazzieri, F Furlan, S D'Alessio, E Zonari & F Blasi

  2. Institute of Genetics and Biophysics, CNR, Naples, Italy

    F Talotta & P Verde

  3. IFOM, FIRC Institute of Molecular Oncology, Milano, Italy

    F Blasi

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  1. R Mazzieri
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Correspondence to F Blasi.

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Mazzieri, R., Furlan, F., D'Alessio, S. et al. A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts. Oncogene 26, 725–732 (2007). https://doi.org/10.1038/sj.onc.1209833

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