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

Mazzieri, R., Furlan, F., D'Alessio, S., Zonari, E., Talotta, F., Verde, P. and Blasi, F. (2007) A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts. Oncogene, 26 5: 725-732. doi:10.1038/sj.onc.1209833


Author Mazzieri, R.
Furlan, F.
D'Alessio, S.
Zonari, E.
Talotta, F.
Verde, P.
Blasi, F.
Title A direct link between expression of urokinase plasminogen activator receptor, growth rate and oncogenic transformation in mouse embryonic fibroblasts
Journal name Oncogene   Check publisher's open access policy
ISSN 0950-9232
1476-5594
Publication date 2007-02-01
Year available 2006
Sub-type Article (original research)
DOI 10.1038/sj.onc.1209833
Open Access Status Not yet assessed
Volume 26
Issue 5
Start page 725
End page 732
Total pages 8
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
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.
Keyword Cell proliferation
E1A
Ink4a
Ras
Urokinase receptor
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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