Home  About us  Contact
 

Telomerase Activation (telomerase + activation)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Telomerase activity in small cell esophageal carcinoma

DISEASES OF THE ESOPHAGUS, Issue 2 2001
V. Chow
Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor. [source]

Inhibition of human telomerase reverse transcriptase by nonsteroidal antiinflammatory drugs in colon carcinoma

CANCER, Issue 6 2006
Hua He M.Phil.
Abstract BACKGROUND Telomerase activation, which is observed in most human cancers, plays an important role in carcinogenesis. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase that is essential for telomerase activity. The aim of the study was to investigate whether nonsteroidal antiinflammatory drugs (NSAIDs) inhibit telomerase activity and hTERT. METHODS Four colon carcinoma cell lines, HT-29, COLO205, CRL-2134, and SW1116, were used in the experiments. Polymerase chain reaction-based telomeric repeat amplification (TRAP) enzyme-linked immunosorbent assay (ELISA) was used to measure telomerase activity in the cells after treatment with aspirin, indomethacin, or SC-236 (a specific cyclooxygenase-2 [COX-2] inhibitor). Expression of hTERT mRNA and protein was detected by reverse transcription,polymerase chain reaction (RT-PCR) and Western blotting, respectively. The dual luciferase reporter assay was performed to identify the potential cis-response elements to NSAIDs in the promoter region of hTERT. RESULTS Aspirin, indomethacin, and SC-236 inhibited telomerase activity in HT-29, COLO205, and CRL-2134 cell lines, but not in the SW1116 cell line. NSAIDs inhibited hTERT mRNA and protein expression through suppression of hTERT transcriptional activity. The hTERT promoter fragment ,145 to ,330 basepairs (bp) upstream of the ATG starting site was sufficient to respond to the NSAID-induced inhibitory effect and the inhibition was COX-2-independent. CONCLUSION NSAIDs inhibit telomerase activity at hTERT transcriptional, mRNA, and protein levels in colon carcinoma cells. The hTERT promoter fragment ,145 to ,330 bp may be the cis-response element to NSAIDs. Cancer 2006. © 2006 American Cancer Society. [source]

Amplification of the telomerase reverse transcriptase (hTERT) gene in cervical carcinomas

GENES, CHROMOSOMES AND CANCER, Issue 3 2002
Anju Zhang
The expression of telomerase reverse transcriptase (hTERT), the catalytic component of the telomerase complex, is required for activation of telomerase during immortalization and transformation of human cells. However, the biochemical and genetic mechanisms governing hTERT expression remain to be elucidated. In the present study, we examined hTERT amplification as a potential genetic event contributing to telomerase activation in cervical carcinomas. An amplification of the hTERT gene was found in 1/4 cervical cancer cell lines and 21/88 primary tumor samples derived from the patients with cervical carcinomas. An increase in the hTERT copy number was significantly correlated with higher levels of hTERT protein expression. Moreover, the hTERT alterations with the enhanced hTERT expression were exclusively observed in those tumors with high-risk human papillomavirus infection. Taken together, the hTERT gene amplification, directly or indirectly targeted by human papillomavirus, may be one of the driving forces responsible for upregulation of hTERT expression and activation of telomerase in cervical cancers. © 2002 Wiley-Liss, Inc. [source]

Oxidative stress may enhance the malignant potential of human hepatocellular carcinoma by telomerase activation

LIVER INTERNATIONAL, Issue 6 2009
Taichiro Nishikawa
Abstract Background/Aims: Continuous oxidative stress (OS) plays an important role in the progression of chronic liver diseases and hepatocarcinogenesis through telomere shortening in hepatocytes. However, it has not been established how the OS influences the progression of human hepatocellular carcinomas (HCCs). We examined the correlations of OS with telomere length of cancer cells, telomerase activity and other clinicopathological factors in 68 HCCs. Methods: The level of 8-hydroxy-2,-deoxyguanosine (8-OHdG) as a marker of OS was examined immunohistochemically and OS was scored in four grades (0,3). The telomere length of cancer cells was measured by quantitative fluorescence in situ hybridization. Telomerase activity was measured by (i) immunodetection of human telomerase reverse transcriptase (hTERT) and (ii) telomere repeat amplification protocol (TRAP) assay. Telomerase related proteins, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Akt, and other clinicopathological factors were also evaluated. Results: As the OS grade increased, the average telomere length became significantly shorter in HCCs, especially in the hTERT-negative group. In the state of high-grade OS, hTERT-positive HCC cells showed more proliferative and less apoptotic features compared with hTERT-negative HCC cells. Telomerase activity, as measured by the TRAP assay, was strongly correlated with OS grade in HCCs. Furthermore, a high OS grade was correlated with the downexpression of PTEN and the activation of Akt. Conclusions: Oxidative stress enhanced the malignant potential of HCCs through the activation of telomerase, which raises the possibility of using OS as a marker for assessing the clinical state of HCCs. [source]