<i>hTERT</i> gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

Palmqvist, Richard; Zhang, Anju; Xu, Dawei; Golovleva, Irina; Norrbäck, Karl-Fredrik; Gruber, Astrid; Öberg, Åke; Stenling, Roger; Roos, Göran

doi:10.1002/ijc.21020

Cited by 16 publications

(18 citation statements)

References 26 publications

(30 reference statements)

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“…Insufficient hTR up-regulation could be one of the explanations for the previously observed nonassociation between hTERT amplification and telomerase activity in some tumors (10)(11)(12)(13). Our study is the first to examine the expression of other telomerase components, hTR and dyskerin, in the context of hTERT-immortalized HMECs, and provides further direct evidence that hTR is limiting for telomerase activity and telomere length maintenance.…”

Section: Discussionsupporting

confidence: 51%

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Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

et al. 2008

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Activation of telomerase is a crucial step during cellular immortalization, and in some tumors this results from amplification of the human telomerase reverse transcriptase (hTERT) gene. Immortalization of normal human cells has been achieved by transduction with hTERT cDNA under the control of a strong heterologous enhancer/promoter, but this is sometimes an inefficient process, with periods of poor growth or even crisis occurring before immortalization. Here, we showed that normal human mammary epithelial cells expressing exogenous hTERT amplified the transgene extensively and expressed high levels of hTERT mRNA and protein. Paradoxically, the cells had low levels of telomerase activity and very short telomeres, indicating that telomerase activity did not correlate with hTERT expression. These cells contained only f20 human telomerase RNA (hTR) molecules/cell (compared with f120 hTR molecules per 293 cell). Expression of exogenous hTR caused increased telomerase activity and telomere lengthening. These data indicate that some hTERTtransduced normal cells may express high levels of the transgene but fail to up-regulate endogenous hTR expression sufficiently to enable expression of robust levels of telomerase activity. [Cancer Res 2008;68(9):3115-23]

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Section: Discussionsupporting

confidence: 51%

“…9). Amplification of the hTERT gene has been observed in various human cancer cell lines and tumors, and is also thought to be a mechanism of telomerase activation (10)(11)(12)(13).…”

Section: In Ref 7)mentioning

confidence: 99%

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

et al. 2008

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“…31 In the present study, the Trapeze XL Telomerase detection kit (Chemicon International, Temecula, CA) was used to analyze CHAPS extracts from the A498 cell line at 0.5 lg protein of extract/assay. Band intensities were quantified using phosphorimager and Image-Quant software (Molecular Dynamics, Sunnyvale, CA) and the telomerase activity was expressed as total product generated (TPG).…”

Section: Telomerase Activity Determinationmentioning

confidence: 99%

The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma

Sitaram

Cairney

Grabowski

et al. 2009

Intl Journal of Cancer

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DJ-1 is as a novel regulator of the tumor suppressor PTEN with stimulatory effects on PI3K-AKT/PKB signaling, one possible target of which is cMyc. The catalytic unit of the telomerase complex, hTERT, can be activated at different levels, including transcriptionally by cMyc and through phosphorylation by AKT/PKB. The aim of the study was to analyze the putative signaling pathway encompassing DJ-1, cMyc and hTERT in a series of 176 renal cell carcinomas (RCC) and experimentally in cell lines. DJ-1 mRNA expression was significantly elevated in clear cell RCC (ccRCC) compared with in papillary RCC (pRCC; p 5 0.005) and kidney cortex tissue (p < 0.001). ccRCC and pRCC demonstrated higher cMyc RNA levels than in kidney cortex (p < 0.001 for both) as well as increased levels of hTERT RNA (p < 0.001 and p 5 0.011, respectively). DJ-1 was positively correlated to cMyc and hTERT in ccRCC (p < 0.001 and p 5 0.019, respectively), but not in pRCC, indicating that this pathway could have a functional significance in ccRCC. siRNA knock down of DJ-1 induced downregulation of cMyc and hTERT mRNA associated with decreased expression of pAKT and cMyc protein levels. hTERT promoter activity was upregulated after DJ-1 transfection and this upregulation was inhibited after mutation of the cMyc binding sites. These experimental data support the functional link among DJ-1, cMyc and hTERT expression as indicated in the tumor material. Neither DJ-1, cMyc nor hTERT mRNA levels were associated with proliferation (S-phase fraction), telomere length or prognosis in ccRCC. ' UICCKey words: renal cell carcinoma; DJ-1; cMyc; hTERT; telomere length; proliferation; prognosis Renal cell carcinoma (RCC) constitutes a heterogeneous group of tumors regarding cytogenetic aberrations, morphologic appearance and clinical outcome. The WHO classification identifies different morphologic subtypes of sporadic RCC including the three most common types, clear cell (ccRCC), papillary (pRCC) and chromophobe RCC. 1 Each entity shows characteristic cytogenetic abnormalities indicating essential differences between the RCC subtypes regarding the mechanisms leading to tumor development.The phosphatase tensin homologue deleted on chromosome 10 (PTEN) protein is a well known tumor suppressor acting as a negative regulator of the phosphoinositide-3 (PI-3)-kinase pathway including the downstream Protein Kinase B (PKB)/Akt protein. In RCC, an association between decreased PTEN expression and high PKB/Akt activation has been described. 2 A novel protein, DJ-1 (also called Cap1/RS/PARK7), has been proposed to be involved in tumorigenesis by negatively regulating PTEN. 3 DJ-1 was first described as a protein showing a cooperative transforming activity with H-Ras in mouse NIH3T3 cells. 4 Overexpression of DJ-1 has been reported in several malignancies, including breast and lung. 5,6 Further, DJ-1 mRNA expression levels seemed to be associated with survival in lung cancer 3 and elevated levels of circulating DJ-1 and anti-DJ-1 auto-antibodies were detected in breast cance...

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“…In the current study, it was found that hTERT mRNA expressions were higher in tumour tissues than in the normal tissues of almost half of the patients. Palmqvist et al (15) determined a positive telomerase activity in 77%, and varied levels of hTERT mRNA expressions in 91% of cases in their study conducted with colorectal cancer patients. In another study, hTERT expressions were observed in all tumour samples from colorectal cancer patients and found to be significantly higher than those in normal tissues (16).…”

Section: Discussionmentioning

confidence: 99%

Normal and Tumour Tissue mRNA Expressions of Telomerase Complex Genes in Several Types of Cancer

Can¹,

Atalay²,

Miser-Salihoglu³

et al. 2017

Balkan Med J

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Aims:To investigate the changes in mRNA expression levels of telomerase-related significant proteins in several types of cancer.Methods:Human telomerase reverse transcriptase, pontin, reptin and dyskerin expressions were measured in normal and tumour tissues obtained from 26 patients with colorectal, breast and gastric cancers, using the real-time reverse transcriptase-polymerase chain reaction method.Results:For all patients, no significant difference was found in mRNA expressions of human telomerase reverse transcriptase and dyskerin (p>0.05), although their levels in tumour tissues were found to be higher than in normal tissues. However, pontin and reptin mRNA expressions were significantly higher in tumour tissues than in normal tissues (p<0.01). While human telomerase reverse transcriptase showed a high correlation with only pontin (p<0.001) in normal tissues, high positive correlations were observed between human telomerase reverse transcriptase with pontin (p<0.005), reptin (p<0.01) and dyskerin (p<0.01) in tumour tissues.Conclusion:The increased mRNA expressions of all four genes in tumour tissues may suggest a role in cancer development. Correlations of pontin, reptin and dyskerin with human telomerase reverse transcriptase support the hypotheses describing their roles in telomerase complexes.

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hTERT gene copy number is not associated with hTERT RNA expression or telomerase activity in colorectal cancer

Cited by 16 publications

References 26 publications

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

Amplification of Telomerase Reverse Transcriptase Gene in Human Mammary Epithelial Cells with Limiting Telomerase RNA Expression Levels

The PTEN regulator DJ‐1 is associated with hTERT expression in clear cell renal cell carcinoma

Normal and Tumour Tissue mRNA Expressions of Telomerase Complex Genes in Several Types of Cancer

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