Telomerase Activity in Primary Prostate Cancer

Lin, Yi; Uemura, Hiroji; Fujinami, Kiyoshi; Hosaka, Masahiko; Harada, Masaoki; Kubota, Yoshinobu

doi:10.1097/00005392-199703000-00125

Cited by 74 publications

(115 citation statements)

References 13 publications

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“…In some series, telomerase activity was associated with lower grade and lower stage BC [84,90]. Other studies pointed out that both telomerase activity [70] and telomerase expression [126] are associated with higher stage and higher grade [70,90]. Preliminary evidence obtained in cell lines suggest that BC might have TERT promoter mutations [53].…”

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 99%

“…The in vitro biological assessment of the functional consequence of these mutations, studied by promoter luciferase assay, revealed that their presence results in a two to fourfold increase in telomerase expression [50,53]. Since previously published studies reported high levels of TERT expression in the set of tumours with TERT promoter mutations [70,78,111], it is likely that such alterations may represent one of the missing links between telomerase gene regulation/ reactivation.…”

Section: Telomerase Promoter Mutations and Cancermentioning

confidence: 99%

“…Using TRAP assay, telomerase activity has been evaluated in BC; telomerase activity was detected in the majority of the studied tumours in contrast to the absence of activity in the respective normal counterpart samples [70,90]. In some series, telomerase activity was associated with lower grade and lower stage BC [84,90].…”

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 99%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and nonneoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

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Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 99%

Section: Telomerase Promoter Mutations and Cancermentioning

confidence: 99%

Section: Telomerase Promoter Mutations In Bladder Carcinomasmentioning

confidence: 99%

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Telomerase promoter mutations in cancer: an emerging molecular biomarker?

et al. 2014

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“…Indeed, previous in vitro studies have already identified telomerase as a potent tumour-specific promoter, 11,12,30 and 80-90% of adenocarcinoma prostate cells, regardless of stage, are telomerase-positive. [13][14][15][16][17][18] Both the human telomerase RNA (hTR) and the human telomerase reverse transcriptase (hTERT) promoters compared favourably with the strong ubiquitous CMV promoter with respect to their ability to drive the expression of the NAT transgene. In transfected LNCaP cells, the uptake achieved by NAT under the control of the telomerase promoters was similar to that achieved by the neuroblastoma cell line SK-N-BE(2c) which endogenously expresses NAT.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 This is an especially attractive component of gene therapy of prostate cancer since there is increased expression of both the RNA component, human telomerase RNA (hTR), and the protein component, human telomerase reverse transcriptase (hTERT) in cancer cells, including prostate cancer, with little expression in normal cells. [13][14][15][16][17][18] We demonstrate that a targeted tumour-specific radiotherapy/gene therapy strategy with [ 131 I]MIBG for prostate cancer is feasible and could be a promising option for future treatment of prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate

Fullerton

Boyd

Mairs

et al. 2004

Prostate Cancer Prostatic Dis

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A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [ 131 I]meta-iodobenzylguanidine ([ 131 I]MIBG), would restrict the effects of radiotherapy to malignant cells, thereby increasing efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were transfected with a transgene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters, enabling them to actively take up [ 131 I]MIBG. This led to tumour-specific cell kill. This strategy has the advantage of generating a radiological bystander effect, leading to the destruction of neighbouring tumour cells that have escaped transfection. This targeted approach could be a promising tumour-specific treatment option for prostate cancer.

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