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

作者：Mazzieri R; Furlan F; D'Alessio S; Zonari E; Talotta F; Verde P; Blasi F^*

来源：Oncogene, 2007, 26(5): 725-732.

DOI：10.1038/sj.onc.1209833

• urokinase receptor
• cell proliferation
• Ras
• E1A
• Ink4a

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-Ras(V12) 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.

• 出版日期2007-2