The secreted protein S100A7 (psoriasin) is induced by telomere dysfunction in human keratinocytes independently of a DNA damage response and cell cycle regulators.

Background: Replicative senescence is preceded by loss of repeat sequences of DNA from the telomeres that eventually leads to telomere dysfunction, the accumulation of irreparable DNA double strand breaks and a DNA damage response (DDR). However, we have previously reported that whilst telomere dysfunction in human keratinocytes is associated with a permanent cell cycle arrest, the DDR was very weak and transcriptional profiling also revealed several molecules normally associated with keratinocytes terminal differentiation, including S100A7 (psoriasin).

Results: We show here that S100A7 and the closely related S100A15 (koebnerisin) are not induced by repairable or irreparable DSBs, ruling out the hypotheses that these genes are induced either by the low DDR observed or by non-specific cell cycle arrest.

Gamma tubulin: a promising indicator of recurrence in squamous cell carcinoma of the larynx.

Objective: Centrosome amplification as detected by gamma tubulin (GT) immunostaining is associated with genetic instability and tumor aggressiveness. We assessed GT for its ability to predict recurrence of squamous cell carcinoma of the larynx (SCCL).

Study Design: Case series with chart review.

Telomere dysfunction in human keratinocytes elicits senescence and a novel transcription profile.

The uncapping of telomeres has been shown to precipitate senescence in normal human fibroblasts and apoptosis in lymphocytes and p53-competent cancer cell lines. However, the effects of telomere uncapping on normal epithelial cells have not previously been examined. We have used the well characterised telomere repeat binding factor 2 (TRF2) dominant-negative mutant, TRF2(DeltaBDeltaM), to deplete Normal Human Epidermal Keratinocytes (NHEK) telomeres of TRF2.

Anticancer therapy targeting telomeres and telomerase : current status.

Normal human somatic cells undergo telomeric attrition causing replicative senescence. Most immortal cancer cells cope with this by upregulating the active form of telomerase. Long-term inhibition of telomerase results in telomeric attrition and highly specific killing of cancer cells, in which the maintenance of telomere length is reliant on telomerase activity.

Telomere dysfunction is related to the intrinsic radio-resistance of human oral cancer cells.

Evidence from telomerase-deficient mice strongly suggests that dysfunctional short telomeres affect cellular radio-sensitivity but this idea has yet to be extensively tested in relevant human cancer types such as oral squamous cell carcinomas (OSCCs), which are frequently treated by radiotherapy. The OSCC line BICR7 has low levels of telomerase activity, short telomeres and high levels of telomere dysfunction (judged by a high level of anaphase bridges); whereas the BICR6 line has high levels of telomerase and is more radio-resistant. Ectopic expression of the human TElomerase Reverse Transcriptase (hTERT) reduced telomere dysfunction and increased radio-resistance in BICR7 cells, but not BICR6.