A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics.

Molecular Cancer
Giampiero PorcuAntonella Ragnini-Wilson

Abstract

Farnesyltransferase inhibitors (FTIs) are anticancer agents developed to inhibit Ras oncoprotein activities. FTIs of different chemical structure act via a conserved mechanism in eukaryotic cells. They have low toxicity and are active on a wide range of tumors in cellular and animal models, independently of the Ras activation state. Their ultimate mechanism of action, however, remains undetermined. FTase has hundred of substrates in human cells, many of which play a pivotal role in either tumorigenesis or in pro-survival pathways. This lack of knowledge probably accounts for the failure of FTIs at clinical stage III for most of the malignancies treated, with the notable exception of haematological malignancies. Understanding which cellular pathways are the ultimate targets of FTIs in different tumor types and the basis of FTI resistance is required to improve the efficacy of FTIs in cancer treatment. Here we used a yeast-based cellular assay to define the transcriptional changes consequent to FTI peptidomimetic administration in conditions that do not substantially change Ras membrane/cytosol distribution. Yeast and cancer cell lines were used to validate the results of the network analysis. The transcriptome of yeast cells tre...Continue Reading

References

Nov 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·J HirschmanS Kustu
Mar 8, 1996·The Journal of Biological Chemistry·P J Casey, M C Seabra
Feb 16, 2000·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J ZujewskiK H Cowan
Jan 16, 2002·The Journal of Biological Chemistry·Masatsugu TanakaYoshiaki Ishigatsubo
Jun 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M CrulJ H M Schellens
Sep 5, 2002·Molecular Microbiology·Anja SchmidtMichael N Hall
Nov 29, 2002·The EMBO Journal·Wolfgang WagnerAntonella Ragnini-Wilson
Jul 17, 2003·International Journal of Cancer. Journal International Du Cancer·Sophie F Doisneau-SixouRobert L Sutherland
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kristin BaetzMichel Roberge
May 15, 2004·Stroke; a Journal of Cerebral Circulation·Mitsuo YamaguchiJohn H Zhang
Aug 11, 2004·Cell Cycle·Elisabetta CameroniClaudio De Virgilio
Aug 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yoonjung KhoYingming Zhao
Sep 24, 2005·The Oncologist·Natalie M G M AppelsJan H M Schellens
Nov 10, 2005·Journal of Lipid Research·Andrea D BassoW Robert Bishop
Mar 6, 2007·Nature Genetics·Ethan O PerlsteinLeonid Kruglyak
Apr 4, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mitch RaponiDavid Atkins
Jun 15, 2007·Molecular Cell·Jörg UrbanRobbie Loewith
Jul 3, 2007·Biochimica Et Biophysica Acta·Raymond E Chen, Jeremy Thorner
Jul 10, 2007·Cell Metabolism·Ted Powers
Jul 11, 2007·Molecular Cancer Therapeutics·Kazuhiro KatayamaYoshikazu Sugimoto
Oct 5, 2007·The Journal of Investigative Dermatology·Magdalena KarbowniczekElizabeth P Henske
Nov 6, 2007·Journal of Cellular and Molecular Medicine·Marian E DurkinNicholas C Popescu
Nov 4, 2008·Journal of Agricultural and Food Chemistry·Patrick P McCue, James M Phang
Apr 9, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Joseph A SparanoSaid M Sebti
Aug 27, 2009·Biologics : Targets & Therapy·Judith E Karp, Jeffrey E Lancet

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Datasets Mentioned

BETA
GGTI298

Methods Mentioned

BETA
Fluorescence
PCR
fluorescence microscopy
GTPase
X-ray
chip
electrophoresis
FCS

Software Mentioned

GO
ScanR
Primer Express
SGD
work
Acuity
GoTerm Process
GenePix6
Super GO - Slim Component GO - Slim Process
Olympus

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