A Direct Link Between Expression of Urokinase Plasminogen Activator Receptor, Growth Rate and Oncogenic Transformation in Mouse Embryonic Fibroblasts.
From: Department of Molecular Biology and Functional Genomics, Università Vita Salute San Raffaele, Milano, Italy.
Oncogene
- Publish Date: Feb 2007
- ISSN: 0950-9232
- Volume: 26
- Issue: 5
- Pages: 725-32
- Medium: Print
- Language: English
- Citation (JAMA): 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 Feb 2007;26:725-32
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-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.
Mesh Headings (Keywords): Animals, Apoptosis, Cell Proliferation, Cell Transformation, Neoplastic, Cells, Cultured, Cyclin-Dependent Kinase Inhibitor p16, Embryo, Mammalian, Fibroblasts, Gene Expression Regulation, Homozygote, Mice, Mice, Knockout, Mice, Nude, Mitogen-Activated Protein Kinases, Neoplasm Invasiveness, Oncogene Protein p21(ras), Receptors, Cell Surface, Transcription Factor AP-1, Transduction, Genetic, Transfection, Vitronectin
Check for Full Text / PubMed Unique Identifier (PMID): 16878153
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.