Correlation between radiation-induced telomerase activity and human telomerase reverse transcriptase mRNA expression in HeLa cells

Satra, Maria; Tsougos, Ioannis; Papanikolaou, Vasilis K.; Theodorou, K.; Kappas, C.; Tsezou, Ass. Prof. Aspasia

doi:10.1080/09553000600800090

Cited by 12 publications

(14 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The stability of hTERT transcript was preserved up to dose of 8 Gy, beyond which reduction in the transcript was observed together with decline in proliferation probably due to general damage induced by irradiation. Consistent with these results, two other studies have shown similar results in AML mice model and in HeLa cells (24,27). One study reported an increase in hTERT expression after irradiation but at different time points (15) relatively to the increase in TA.…”

Section: Discussionsupporting

confidence: 78%

“…Most of the studies addressing this issue are consistent with our results showing upregulation of TA after irradiation (14,15,24,25). Several reports, however, describe down-regulation of TA (12,26), sometimes after very high irradiation dosages (20-160 Gy), which probably nonspecifically destroyed cellular proteins (13,27). In another study, mouse sarcoma cells were used and the differences may stem from different telomere biology between human and murine cells (28).…”

Section: Discussionsupporting

confidence: 77%

See 1 more Smart Citation

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ram

Uziel²,

Eldan³

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose:Telomerase is considered currently as a hallmark of cancer, and its inhibition is expected to become an important anticancer modality. In contrast to abundant data concerning the effect of cytotoxic drugs on telomerase activity (TA), there is scant information on the effect of radiation on telomerase.The mechanism of telomerase regulation by irradiation has never been evaluated in detail. In the present study, we investigated the effect of radiation onTA and its regulation in cancer cells. Experimental Design:The effect of various radiation doses onTA in several malignant and nonmalignant cell lines was evaluated. All malignant cells exhibited similar telomerase response to radiation and its regulation was assessed at transcriptional and post-translational levels in K562 cells. Next step was the evaluation of the upstream signaling pathways leading to changes inTA using kinetics and specific inhibitors. Results: Radiation up-regulated TA in dose-dependent manner only in cancer cells. Telomerase was activated by phosphorylation by Akt and by cytoplasmic-nuclear shift. Transcriptional processes were not involved inTA. This telomerase regulation is mediated by Ras/phosphatidylinositol 3-kinase/Akt pathway. The canonical membrane effectors of irradiation (epidermal growth factor receptor, insulin-like growth factor-I receptor, and Ca 2+ influx) were not involved in this process. Conclusions: Radiation up-regulates telomerase activity specifically in cancer cells. This study adds to accumulating evidence pointing to post-translational level as important mode of telomerase regulation. Telomerase activation due to radiation may be detrimental in treatment of cancer. Data described in this study may add to future interventions aiming at inhibition of telomerase activation during irradiation.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 77%

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ram

Uziel²,

Eldan³

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…It has been confirmed that the highest rate of telomerase activity is at S phase, whereas the lowest is at the G2/M phase [23]. Thus, our data indicate that the G2/M phase blockage is largely responsible for the antisense gene-mediated down-regulation of telomerase activity, which is in agreement with results from previous investigations [24][25][26].…”

Section: Discussionsupporting

confidence: 94%

The Retrovirus-mediated Antisense Human Telomerase RNA (hTR) Gene Limits the Growth of Hepatocellular Carcinoma Growth in Cell Culture and Animals

Liu

Zhu

et al. 2007

Dig Dis Sci

View full text Add to dashboard Cite

show abstract

“…Cells in exponential growth were irradiated with 10 and 20 Gy doses of ionizing radiation, using a 6MV photon linear accelerator with a dose rate of 4.90 Gy/min at room temperature. Ten and 20 Gy doses were chosen based on our previous dose titration data (20). Two separate experiments were carried out for each cell line studied.…”

Section: Methodsmentioning

confidence: 99%

“…In order to ensure a uniform dose build-up and homogeneous irradiation cells were situated at the isocenter of two tangential opposed photon fields of 20x20 field size. For the accurate positioning and immobilization of the culture plates and flasks and to ensure reproducibility and accurate doses of irradiation, a homogeneous polymethyl methacrylate C 5 H 8 O 2 (PPMA) phantom was constructed, as previously described by us (20).…”

Section: Methodsmentioning

confidence: 99%

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

Papanikolaou

Iliopoulos²,

Dimou³

et al. 2009

Int J Oncol

View full text Add to dashboard Cite

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 ER· 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.

show abstract

Correlation between radiation-induced telomerase activity and human telomerase reverse transcriptase mRNA expression in HeLa cells

Abstract: A correlation between TA and hTERT mRNA expression and a radiation induced cell cycle dependent modification of hTERT mRNA expression was established for the first 24 h post-irradiation.

Cited by 12 publications

References 29 publications

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

Ionizing Radiation Up-regulates Telomerase Activity in Cancer Cell Lines by Post-translational Mechanism via Ras/Phosphatidylinositol 3-Kinase/Akt Pathway

The Retrovirus-mediated Antisense Human Telomerase RNA (hTR) Gene Limits the Growth of Hepatocellular Carcinoma Growth in Cell Culture and Animals

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

Contact Info

Product

Resources

About