The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells

  • Authors:
    • Vassilis Papanikolaou
    • Dimitrios Iliopoulos
    • Ioannis Dimou
    • Stephanie Dubos
    • Ioannis Tsougos
    • Kyriaki Theodorou
    • Sofia Kitsiou-Tzeli
    • Aspasia Tsezou
  • View Affiliations

  • Published online on: November 1, 2009     https://doi.org/10.3892/ijo_00000430
  • Pages: 1141-1149
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Abstract

Cancer cell characteristics may play a pivotal role in the response to therapy by activating or deactivating different molecular pathways. In the present study, we investigated the implication of breast cancer cell features, such as HER2 and p53 in the activation of telomerase upon exposure to ionizing radiation. Telomerase is among the most important cancer biomarkers, conferring to tumor cells unlimited proliferative capacity, increased survival potential and resistance to several types of cellular stress. We investigated possible mechanisms regulating telomerase in six irradiated breast cancer cell lines (MCF-7, MCF-7/HER2, MDA-MB-231, SK-BR-3, BT-474 and HBL-100) differing in their HER2, p53 and ERα status. hTERT mRNA expression was evaluated by real-time PCR and telomerase activity by the TRAP assay. HER2, c-myc, p53 and p21 protein levels were evaluated by Western blotting. Silencing of hTERT and HER2 was achieved by small interfering RNA technology. Chromatin immunoprecipitation was used to evaluate H3 histone acetylation status, as well as myc/mad/max and p53 transcription factors interaction with the hTERT promoter. Our results showed for the first time, that only HER2-positive cells, independently of their p53 status, upregulated hTERT/telomerase, while knockdown of hTERT increased radio-sensitivity. Knockdown of HER2 also led to increased radio-sensitivity and downregulation of hTERT/telomerase. We also demonstrated that c-myc and mad1 regulate hTERT expression in all irradiated breast cancer cells. We conclude, for the first time, that HER2 phenotype upregulates hTERT through c-myc activation and confers radio-resistance to breast cancer cells.

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November 2009
Volume 35 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Papanikolaou V, Iliopoulos D, Dimou I, Dubos S, Tsougos I, Theodorou K, Kitsiou-Tzeli S and Tsezou A: The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells. Int J Oncol 35: 1141-1149, 2009.
APA
Papanikolaou, V., Iliopoulos, D., Dimou, I., Dubos, S., Tsougos, I., Theodorou, K. ... Tsezou, A. (2009). The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells. International Journal of Oncology, 35, 1141-1149. https://doi.org/10.3892/ijo_00000430
MLA
Papanikolaou, V., Iliopoulos, D., Dimou, I., Dubos, S., Tsougos, I., Theodorou, K., Kitsiou-Tzeli, S., Tsezou, A."The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells". International Journal of Oncology 35.5 (2009): 1141-1149.
Chicago
Papanikolaou, V., Iliopoulos, D., Dimou, I., Dubos, S., Tsougos, I., Theodorou, K., Kitsiou-Tzeli, S., Tsezou, A."The involvement of HER2 and p53 status in the regulation of telomerase in irradiated breast cancer cells". International Journal of Oncology 35, no. 5 (2009): 1141-1149. https://doi.org/10.3892/ijo_00000430