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Telomerase activation has recently been linked to malignant progression of human tumors. A series of benign, atypical, and anaplastic/malignant meningiomas have been investigated by the authors for telomerase production and the telomerase catalytic subunit human telomerase reverse transcriptase. In seven of eight of 34 benign patients, but in nine of 12 atypical and seven of seven anaplastic/malignant meningiomas was found, with a quantitative repeat amplification technique used to measure telomerase enzyme activity. The catalytic subunit hTERT gene was present in 11 of 33 patients, 12 of 13 atypical, and all seven anaplastic/malignant tumors. All telomerase-positive lesions were also positive for hTERT mRNA, while no telomerase activity was detected in six of 29 hTERT-positive tumors. In the majority of meningiomas, upregulation of hTERT is the rate-limiting step for telomerase activation. In all four tumors with gross brain injury, expression of telomeraserase and hTERT was seen.
Source link: https://doi.org/10.3171/jns.2000.92.5.0832
In cultured human mammary epithelial cells lacking both telomerase activity and p16 INK4A, a functional human telomerase catalytic subunit, hTERT, resulted in increased growth in the absence and presence of TGF-u03b2. TGF-u03b2 resistance can be triggered by the ability of ectopic hTERT to induce TGF-u03b2 resistance in rare carcinogen-treated HMEC. This interaction of hTERT may represent a major change that occurs during in vivo human breast carcinogenesis.
Source link: https://doi.org/10.1073/pnas.071483998
ABSTRACT We have mapped the 5u2032 and 3u2032 boundaries of the human telomerase RNA region that is required to produce activity with the human protein catalytic subunit by using in vitro assembly methods obtained from rabbit reticulocyte lysates and human cell extracts to establish activity with the human protein catalytic subunit. In addition, we found two strands of hTR that do not produce telomerase activity when mixed with hTERT, but they can both function together to produce active telomerase.
Source link: https://doi.org/10.1128/mcb.19.9.6207
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