Telomerase activity and expression of telomerase genes in squamous dysplasia and squamous cell carcinoma of the esophagus

Summary Aberrations in telomere length and telomere maintenance contribute to cancer development. In this article, we review basic principles of telomere length in normal and tumor tissue and the presence of the two main telomere maintenance pathways as they pertain to GI tract cancer. Peripheral blood telomeres are shorter in patients with many types of GI tract cancers. Telomere length in tumor DNA also appears to shorten early in cancer development. Tumor telomere shortening is often accompanied by telomerase activation to protect genetically damaged DNA from normal cell senescence or apoptosis, allowing immortalized but damaged DNA to persist. Alternative lengthening of telomeres (ALT) is another mechanism used by cancer to maintain telomere length in cancer cells. Telomerase and ALT activators and inhibitors may become important chemopreventive or chemotherapeutic agents as our understanding of telomere biology, specific telomere related phenotypes, and its relationship to carcinogenesis increases.

show abstract

“…ESCC has increased telomerase activity [91], but activation of telomerase is not related to prognosis in patients with ESCC [92]. …”

Section: The Gi Tract Cancers Telomeres and Telomere Maintenance Mementioning

confidence: 99%

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Basu¹,

Skinner²,

Litzelman³

et al. 2013

Expert Review of Gastroenterology & Hepatology

View full text Add to dashboard Cite

show abstract

“…Previously, telomerase activity has been identified in tumor initiating cells (3,18). Telomerase has been reported to be expressed in 86.2% esophageal carcinoma tissues; however, healthy esophageal tissue did not express it (19). Therefore, this suggests that there may be a window for telomerase inhibition-based treatment.…”

Section: Discussionmentioning

confidence: 99%

Azidothymidine inhibits cell growth and telomerase activity and induces DNA damage in human esophageal cancer

Wang

Zhou

et al. 2017

Molecular Medicine Reports

View full text Add to dashboard Cite

Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE-11. A telomeric repeat amplification assay was utilized to detect telomerase activity following treatment of TE-11 cells with AZT. The effect of AZT on TE-11 cell cycle distribution was determined by flow cytometry. Cellular DNA damage was evaluated by a comet assay and an MTT assay demonstrated that AZT significantly inhibited the viability of TE-11 cells, in a time-and dose-dependent manner. In addition, TE-11 cells treated with various concentrations of AZT exhibited a significant reduction in telomerase activity and percentage of cells in the G1/G0 phase, and an increase in the percentage of cells in the S phase. High doses of AZT caused DNA damage, and enhanced the expression levels of γ-H2A histone family member X and phosphorylated checkpoint kinase 2 in TE-11 cells. These results demonstrated that AZT effectively inhibits proliferation of the TE-11 human esophageal cancer cell line in vitro. The growth inhibitory effects were associated with a reduction in telomerase activity, S and G2/M phase cell cycle arrest, and enhanced DNA damage, suggesting that AZT may be utilized in the clinic for the treatment of esophageal cancer.

show abstract

“…In a recent issue of the Journal of Surgical Oncology, Dr. Yu et al [1] report that increased telomerase activity was found in squamous dysplasia (44.7%) and carcinoma of the esophagus (86.2%), but not in normal esophageal tissue (0%). These data indicate that telomerase activation might play a role in esophageal carcinogenesis including the early pre-malignant dysplasia.…”

Section: Telomeres Arementioning

confidence: 99%

Telomerase: A potential molecular marker and therapeutic target for cancer

Chang

2004

Journal of Surgical Oncology

View full text Add to dashboard Cite

Telomerase activity and expression of telomerase genes in squamous dysplasia and squamous cell carcinoma of the esophagus

Cited by 25 publications

References 30 publications

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Telomeres and telomere dynamics: relevance to cancers of the GI tract

Azidothymidine inhibits cell growth and telomerase activity and induces DNA damage in human esophageal cancer

Telomerase: A potential molecular marker and therapeutic target for cancer

Contact Info

Product

Resources

About