PPARgamma ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network, in colon cancer cells. (Articolo in rivista)

Type
Label
  • PPARgamma ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network, in colon cancer cells. (Articolo in rivista) (literal)
Anno
  • 2010-01-01T00:00:00+01:00 (literal)
Alternative label
  • Toaldo C. 1, Pizzimenti S. 1, Cerbone A. 1, Pettazzoni P. 1, Menegatti E. 2, Daniela B. 2, Minelli R. 1, Giglioni B. 3, Dianzani M.U. 1, Ferretti C. 4, Barrera G. 1 (2010)
    PPARgamma ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network, in colon cancer cells.
    in Journal of Cellular and Molecular Medicine (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Toaldo C. 1, Pizzimenti S. 1, Cerbone A. 1, Pettazzoni P. 1, Menegatti E. 2, Daniela B. 2, Minelli R. 1, Giglioni B. 3, Dianzani M.U. 1, Ferretti C. 4, Barrera G. 1 (literal)
Pagina inizio
  • 1347 (literal)
Pagina fine
  • 1357 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 14 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • Pubblicato on-line: 13 Novembre 2009. Corresponding author: Cristina Toaldo (cristina.toaldo@unito.it) IF 2010: 4.608 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Section of General Pathology, Department of Medicine and Experimental Oncology, University of Torino, Torino. 2. Section of Clinical Pathology, Department of Experimental Medicine and Oncology, University of Torino, Torino. 3. Institute of Molecular Bioimaging and Physiology–CNR, University of Milano-Bicocca, Scientific Institute San Raffaele, Milano 4. Department of Anatomy, Pharmacology, and Forensic Medicine, University of Torino, Torino. (literal)
Titolo
  • PPARgamma ligands inhibit telomerase activity and hTERT expression through modulation of the Myc/Mad/Max network, in colon cancer cells. (literal)
Abstract
  • Abstract In human cells the length of telomeres depends on telomerase activity. This activity and the expression of the catalytic subunit of telomerase (hTERT) is strongly up-regulated in most human cancers. hTERT expression is regulated by different transcription factors, such as c-Myc, Mad1 and Sp1. In this study, we demonstrated that 15d-PG J2 and rosiglitazone (an endogenous and synthetic PPARgamma ligand, respectively) inhibited hTERT expression and telomerase activity in CaCo-2 colon cancer cells. Moreover, both ligands inhibited c-Myc protein expression and its E-box DNA binding activity. Additionally, Mad1 protein expression and its E-box DNA binding activity were strongly increased by 15d-PG J2 and, to a lesser extent, by rosiglitazone. Sp1 transcription factor expression and its GC-box DNA binding activity were not affected by both PPARgamma ligands. Results obtained by transient transfection of CaCo-2 cells with pmaxFP-Green-PRL plasmid constructs containing the functional hTERT core promoter (including one E-box and five GC-boxes) and its E-box deleted sequences, cloned upstream of the GFP reporter gene, demonstrated that 15d-PG J2, and with minor effectiveness, rosiglitazone, strongly reduced hTERT core promoter activity. E-boxes for Myc/Mad/Max binding showed a higher activity than GC-boxes for Sp1. By using GW9662, an antagonist of PPARgamma, we demonstrated that the effects of 15d-PG J2 are completely PPARgamma-independent, whereas the effects of rosiglitazone on hTERT expression seems to be partially PPARgamma-independent. The regulation of hTERT expression by 15d-PG J2 and rosiglitazone, through the modulation of the Myc/Max/Mad1 network, may represent a new mechanism of action of these substances in inhibiting cell proliferation. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Prodotto
Autore CNR di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
Insieme di parole chiave di
data.CNR.it