Biological models and genes of tumor reversion: Cellular reprogramming through tpt1 /TCTP and SIAH-1
Open Access
- 24 October 2002
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 99 (23), 14976-14981
- https://doi.org/10.1073/pnas.222470799
Abstract
Tumor reversion is the process by which some cancer cells lose their malignant phenotype. This study was aimed at defining some of the molecular and phenotypic properties of this process. Biological models of tumor reversion were isolated from human leukemia and breast cancer cell lines by using the H-1 parvovirus as a selective agent. Differential gene expression analysis was performed between the parental malignant cells and their revertants or alternatively between these parental cells and their SIAH-1 transfectant counterparts. These SIAH-1 transfectants have a suppressed malignant phenotype and were used as a control for a viral-free system. Two hundred sixty-three genes were found to be either activated or inhibited during the reversion process, as confirmed by Northern blot analysis or quantitative PCR. Of these, 32% were differentially expressed in all systems, irrespective of whether parvovirus-selected, SIAH-1 overexpressing, or p53 mutant or wild-type cell lines were used, suggesting the existence of a universal mechanism underlying tumor reversion. Translationally Controlled Tumor Protein (tpt1/TCTP) has the strongest differential expression, down-regulated in the reversion of U937- and SIAH-1-overexpressing cells. Inhibition of TCTP expression by anti-sense cDNA or small interfering RNA molecules results in suppression of the malignant phenotype and in cellular reorganization, similar to the effect of SIAH-1. Hence, tumor reversion can be defined at the molecular level, not just as the reversal of malignant transformation, but as a biological process in its own right involving a cellular reprogramming mechanism, overriding genetic changes in cancer, by triggering an alternative pathway leading to suppression of tumorigenicity.Keywords
This publication has 33 references indexed in Scilit:
- Modulation of Transforming Growth Factor β (TGFβ)/Smad Transcriptional Responses through Targeted Degradation of TGFβ-inducible Early Gene-1 by Human Seven in Absentia HomologuePublished by Elsevier ,2002
- Characterization of Fortilin, a Novel Antiapoptotic ProteinJournal of Biological Chemistry, 2001
- Gene expression analysis by massively parallel signature sequencing (MPSS) on microbead arraysNature Biotechnology, 2000
- Mammalian homologs of seven in absentia regulate DCC via the ubiquitin–proteasome pathwayGenes & Development, 1997
- Differential Display of Eukaryotic Messenger RNA by Means of the Polymerase Chain ReactionScience, 1992
- Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6Nature, 1991
- seven in absentia, a gene required for specification of R7 cell fate in the Drosophila eyeCell, 1990
- A ras-related gene with transformation suppressor activityCell, 1989
- Minute virus of mice inhibits cell transformation by simian virus 40Nature, 1982
- Lack of Oncogenic Effect of the H-Viruses for HamstersNature, 1967