Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

Telomerase is a reverse transcriptase associated with cellular immortality through telomere maintenance. This enzyme is activated in 90% of human cancers, and inhibitors of telomerase are currently in clinical trials to counteract tumor growth. Many aspects of telomerase biology have been investigated for therapy, particularly inhibition of the enzyme, but little was done regarding its subcellular shuttling. We have recently shown that mutations in the nuclear export signal of hTERT, the catalytic component of telomerase, led to a mutant (NES-hTERT) that failed to immortalize cells despite nuclear localization and catalytic activity. Expression of NES-hTERT in primary fibroblast resulted in telomere-based premature senescence and mitochondrial dysfunction. Here we show that expression of NES-hTERT in LNCaP, SQ20B and HeLa cells rapidly and significantly decreases their proliferation rate and ability to form colonies in soft agar while not interfering with endogenous telomerase activity. The cancer cells showed increased DNA damage at telomeric and extra-telomeric sites, and became sensitive to ionizing radiation and hydrogen peroxide exposures. Our data show that expression of NES-hTERT efficiently counteracts cancer cell growth in vitro in at least two different ways, and suggest manipulation with the NES of hTERT or its subcellular shuttling as a new strategy for cancer treatment

L’accentuation de la langue bretonne

In this study of Breton accentuation, we are not simply looking for the place of the accent (penultimate, ultieth, etc.), but for distinguishable accentual units. To what extent are accentual units not only distinguishable, but also distinctive? On the basis of distinctive (or at least distinguishable) accentual units, we will propose a phonology of Breton that is no longer based on the word, but on the accentual group. Our hypothesis is that the accentual group is fundamental to the entire phonetic-phonology of Breton

L’accentologie comparée des langues celtiques

Pilch Herbert. L’accentologie comparée des langues celtiques. In: Etudes Celtiques, vol. 29, 1992. Actes du IXe congrès international d'études celtiques. Paris, 7-12 juillet 1991. Deuxième partie : Linguistique, littératures. p. 490

L’accentologie comparée des langues celtiques

Pilch Herbert. L’accentologie comparée des langues celtiques. In: Etudes Celtiques, vol. 29, 1992. Actes du IXe congrès international d'études celtiques. Paris, 7-12 juillet 1991. Deuxième partie : Linguistique, littératures. p. 490