title: Receptor Ck-dependent signaling regulates hTERT gene transcription.
abstract: BACKGROUND
  Available evidence suggests that the regulation of telomerase activity primarily depends on the transcriptional control of the human telomerase reverse transcriptase (hTERT) gene. Although several activators and repressors of hTERT gene transcription have been identified, the exact mechanism by which hTERT transcription is repressed in normal cells and activated in cancer cells remains largely unknown. In an attempt to identify possible novel mechanisms involved in the regulation of hTERT transcription, the present study examined the role of Receptor Ck, a cell surface receptor specific for cholesterol, in the transcription of hTERT gene in normal human peripheral blood mononuclear cells.
  
  
  RESULTS
  Activated Receptor Ck was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling was also found to down-regulate the mRNA expression of the gene coding for the ligand inducible transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma). The ligand activation of PPARgamma resulted in the down-regulation of c-myc and hTERT mRNA expression. By using specific activator and inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck dependent down-regulation of hTERT gene transcription involved inhibition of PKC. In addition, 25-hydroxycholesterol was found to contribute to the transcriptional regulation of hTERT gene.
  
  
  CONCLUSIONS
  Taken together, the findings of this study present evidence for a molecular link between cholesterol-activated Receptor Ck and hTERT transcription, and provide new insights into the regulation of hTERT expression in normal human peripheral blood mononuclear cells.
authors.affiliation: Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012, India. sikandk@yahoo.com
authors.forename: Kavleen
authors.initials: K
authors.lastname: Sikand
authors.forename: Deepak
authors.initials: D
authors.lastname: Kaul
authors.forename: Neelam
authors.initials: N
authors.lastname: Varma
mesh_terms: D002478:Cells, Cultured; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D019254:Genes, bcl-2 / Q000235:genetics; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D047495:PPAR gamma / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D019098:Telomerase / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D056741:Cyclin D; D016213:Cyclins; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; D047495:PPAR gamma; D012333:RNA, Messenger; D018110:Receptors, Lipoprotein; C113493:receptor-Ck; C007997:25-hydroxycholesterol; D011493:Protein Kinase C; D019098:Telomerase