Τίτλος:
hTERT regulation by NF-κB and c-myc in irradiated HER2-positive breast cancer cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: 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. Materials and 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-κB and c-myc. © 2011 Informa UK, Ltd.
Συγγραφείς:
Papanikolaou, V.
Athanassiou, E.
Dubos, S.
Dimou, I.
Papathanasiou, I.
Kitsiou-Tzeli, S.
Kappas, C.
Tsezou, A.
Περιοδικό:
International Journal of Radiation Biology
Λέξεις-κλειδιά:
epidermal growth factor receptor 2; estrogen receptor alpha; immunoglobulin enhancer binding protein; Max protein; messenger RNA; Myc protein; progesterone receptor; protein kinase B; protein Mad1; small interfering RNA; survivin; telomerase; telomerase reverse transcriptase, apoptosis; article; breast cancer; cancer cell; chromatin immunoprecipitation; clinical article; controlled study; flow cytometry; gene silencing; genetic transfection; human; human cell; human tissue; ionizing radiation; irradiation; priority journal; protein binding; protein expression; quantitative analysis; real time polymerase chain reaction; RNA interference; telomeric repeat amplification protocol; tumor biopsy; upregulation, Apoptosis; Breast Neoplasms; Chromatin Immunoprecipitation; Female; Gene Expression Regulation, Neoplastic; Humans; NF-kappa B; Phenotype; Proto-Oncogene Proteins c-myc; Receptor, erbB-2; Receptors, Estrogen; Receptors, Progesterone; RNA, Messenger; Telomerase; Telomere; Time Factors
DOI:
10.3109/09553002.2011.572112
