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

Journal of Cellular and Molecular Medicine
Cristina ToaldoGiuseppina Barrera

Abstract

In human cells the length of telomeres depends on telomerase activity. This activity and the expression of the catalytic subunit of human telomerase reverse transcriptase (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 peroxisome proliferators activated receptor gamma (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 green fluorescent protein reporter gene, demonstrated that 15...Continue Reading

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Citations

Jul 28, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Marta GladychBlazej Rubis
Oct 2, 2012·PPAR Research·Joo-In Park, Jong-Young Kwak
Jan 22, 2015·Journal of Physiology and Biochemistry·Yang YangWei-Sen Jin
Feb 12, 2017·Frontiers in Cell and Developmental Biology·Ekta Khattar, Vinay Tergaonkar
Apr 16, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Matthew J DurandAndreas M Beyer
May 6, 2016·Nature Communications·Meilin WangJinfei Chen
Nov 12, 2015·World Journal of Gastroenterology : WJG·Sinem Tuncer, Sreeparna Banerjee
Nov 11, 2018·The Science of the Total Environment·Haobin HuangCheng Xu

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Datasets Mentioned

BETA
AF098956

Methods Mentioned

BETA
transfection
Protein assay
PCR

Software Mentioned

hTERT
Multi
Analyst

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