PMID- 17213802 OWN - NLM STAT- MEDLINE DCOM- 20070815 LR - 20181113 IS - 0950-9232 (Print) IS - 1476-5594 (Electronic) IS - 0950-9232 (Linking) VI - 26 IP - 29 DP - 2007 Jun 21 TI - Transcriptomal profiling of the cellular transformation induced by Rho subfamily GTPases. PG - 4295-305 AB - We have used microarray technology to identify the transcriptional targets of Rho subfamily guanosine 5'-triphosphate (GTP)ases in NIH3T3 cells. This analysis indicated that murine fibroblasts transformed by these proteins show similar transcriptomal profiles. Functional annotation of the regulated genes indicate that Rho subfamily GTPases target a wide spectrum of functions, although loci encoding proteins linked to proliferation and DNA synthesis/transcription are upregulated preferentially. Rho proteins promote four main networks of interacting proteins nucleated around E2F, c-Jun, c-Myc and p53. Of those, E2F, c-Jun and c-Myc are essential for the maintenance of cell transformation. Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene expression without affecting the E2F and c-Jun pathways. Loss-of-function studies demonstrate that c-Myc is important for the blockage of cell-contact inhibition rather than for promoting the proliferation of Rho-transformed cells. However, c-Myc overexpression does not bypass the inhibition of cell transformation induced by Rock blockage, indicating that c-Myc is essential, but not sufficient, for Rock-dependent transformation. These results reveal the complexity of the genetic program orchestrated by the Rho subfamily and pinpoint protein networks that mediate different aspects of the malignant phenotype of Rho-transformed cells. FAU - Berenjeno, I M AU - Berenjeno IM AD - Centro de Investigacion del Cancer and Instituto de Biologia Molecular y Celular del Cancer (IBMCC), CSIC-University of Salamanca, Campus Unamuno, Salamanca, Spain. FAU - Nunez, F AU - Nunez F FAU - Bustelo, X R AU - Bustelo XR LA - eng SI - GEO/GSE5913 GR - R01 CA073735/CA/NCI NIH HHS/United States GR - 5R01-CA73735-10/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070108 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (E2F Transcription Factors) RN - 0 (Myc protein, mouse) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Proto-Oncogene Proteins c-myc) RN - EC 3.6.5.2 (Rhoc protein, mouse) RN - EC 3.6.5.2 (ras Proteins) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - EC 3.6.5.2 (rhoB GTP-Binding Protein) RN - EC 3.6.5.2 (rhoC GTP-Binding Protein) SB - IM MH - Amino Acid Substitution/genetics MH - Animals MH - Cell Transformation, Neoplastic/*genetics/*metabolism/pathology MH - E2F Transcription Factors/biosynthesis/genetics MH - *Gene Expression Profiling MH - Mice MH - Multigene Family/*genetics MH - NIH 3T3 Cells MH - Proto-Oncogene Proteins c-jun/biosynthesis/genetics/physiology MH - Proto-Oncogene Proteins c-myc/biosynthesis/genetics/physiology MH - ras Proteins/physiology MH - rho GTP-Binding Proteins/*genetics/physiology MH - rhoA GTP-Binding Protein/physiology MH - rhoB GTP-Binding Protein/physiology MH - rhoC GTP-Binding Protein PMC - PMC2084474 MID - NIHMS22213 EDAT- 2007/01/11 09:00 MHDA- 2007/08/19 09:00 PMCR- 2007/12/21 CRDT- 2007/01/11 09:00 PHST- 2007/01/11 09:00 [pubmed] PHST- 2007/08/19 09:00 [medline] PHST- 2007/01/11 09:00 [entrez] PHST- 2007/12/21 00:00 [pmc-release] AID - 1210194 [pii] AID - 10.1038/sj.onc.1210194 [doi] PST - ppublish SO - Oncogene. 2007 Jun 21;26(29):4295-305. doi: 10.1038/sj.onc.1210194. Epub 2007 Jan 8.