title: hTERT regulation by NF-κB and c-myc in irradiated HER2-positive breast cancer cells.
abstract: OBJECTIVE
  Telomerase activity (TA), frequently observed in cancer, compensates for telomere shortening thus preventing cell senescence and conferring resistance to therapy. In the present study, we investigated the expression of human telomerase reverse transcriptase (hTERT) and TA and their regulation, as well as apoptotic rates and correlation with the presence of human epidermal growth factor receptor 2 (HER2), in irradiated tumour-derived breast cancer cells.
  
  
  METHODS
  In 50 breast cancer tissue samples hTERT mRNA expression and TA were correlated with cell features (HER2, Estrogen and Progesterone Receptor status). Cells from six samples were then irradiated with 10 and 20 Gy; apoptotic rates were measured by flow cytometry, hTERT mRNA expression by real-time polymerase chain reaction and TA by telomeric repeat amplification protocol assay, at 24-144 h post-irradiation. Chromatin immunoprecipitation was performed to investigate hTERT and cellular-myelocytomatosis (c-myc) promoters' activity. HER2 gene knockdown was performed using small interfering RNA technology.
  
  
  RESULTS
  hTERT/TA were found increased only in irradiated HER2-positive cells, which were found to be more radioresistant, while HER2 knockdown led to hTERT/TA downregulation. HER2 was found to mediate hTERT expression through activation of Nuclear Factor-kappa B (NF-κB) and c-myc.
  
  
  CONCLUSIONS
  The present study suggests that following irradiation, HER2 receptor activates hTERT/telomerase, increasing the breast cancer cells' survival potential, through sequential induction of transcription factors NF-κΒ and c-myc.
authors.affiliation: Department of Biology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Papanikolaou
authors.forename: Evangelos
authors.initials: E
authors.lastname: Athanassiou
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dubos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Dimou
authors.forename: Ioanna
authors.initials: I
authors.lastname: Papathanasiou
authors.forename: Sofia
authors.initials: S
authors.lastname: Kitsiou-Tzeli
authors.forename: Constantin
authors.initials: C
authors.lastname: Kappas
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D013997:Time Factors
chemical_list: D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D019098:Telomerase; C509186:TERT protein, human