Julia Skinner

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MRC-5 cells are a well-characterized human diploid fibroblast cell line approved for vaccine production and favoured for the routine propagation of human cytomegalovirus (HCMV). Ectopic expression of telomerase in fibroblasts is capable of overcoming replicative senescence induced by telomere shortening. Following delivery of the hTERT gene to MRC-5 cells(More)
Ras mutations occur as an early event in many human tumours of epithelial origin, including thyroid. Using primary human thyroid epithelial cells to model tumour initiation by Ras, we have shown previously that activation of both the MAP kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) effector pathways are necessary, but even when activated together(More)
Prevention of telomere erosion through acquisition of telomerase activity is thought to be an essential mechanism in most human cancer cells for avoidance of cellular senescence and crisis. It has been generally assumed that once telomerase has been activated, no further telomere shortening should ensue. We show here, however, that a much more complex(More)
Despite several recent studies, the biological status and clinical relevance of telomerase expression in tumours derived from the thyroid follicular cell remain controversial. This study has analysed a series of normal, benign, and malignant thyroid samples using two novel approaches: the use of purified epithelial cell fractions to eliminate(More)
Studies on telomere and telomerase biology are fundamental to the understanding of human ageing, and age-related diseases such as cancer. However, human studies are hampered by the lack of fully reflective animal model systems. Here we describe basic studies of telomere length and telomerase activity in sheep tissues and cells. Terminal restriction fragment(More)
An initiating role for RAS oncogene mutation in several epithelial cancers is supported by its high incidence in early-stage tumors and its ability to induce proliferation in the corresponding normal cells in vitro. Using retroviral transduction of thyroid epithelial cells as a model we ask here: (i) how mutant RAS can induce long-term proliferation in an(More)
The accumulation of senescent fibroblasts within tissues has been suggested to play an important role in mediating impaired dermal wound healing, which is a major clinical problem in the aged population. The concept that replicative senescence in wound fibroblasts results in reduced proliferation and the failure of refractory wounds to respond to treatment(More)
Using microinjection of recombinant protein to directly control 'expression' levels, we have compared the proliferative response to ras oncogene activation in two normal cell types--fibroblast and thyroid epithelial cell--which give rise to human tumours with very low and high frequencies of ras mutation respectively. A concentration-dependent stimulation(More)