Alterations in p53 and p16^INK4 Expression and Telomere Length during Spontaneous Immortalization of Li-Fraumeni Syndrome Fibroblasts

Abstract

INK4 expression and a novel mechanism for the elongation of telomeres.

Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis

“…Avoidance of telomerase shortening by expression of telomerase may contribute to the immortal phenotype. On the other hand, some immortal cell lines without detectable telomerase activity have been described that they are characterized by long telomeres (Rogan et al, 1995;Strahl and Blackburn, 1996). These observations indicate the presence of a telomerase-independent mechanism for telomere length maintenance in these tumors.…”

Identification of candidate alternative lengthening of telomeres genes by methionine restriction and RNA interference

“…Screening for genes required for APB formation, and candidate genes for ALT As is characteristic of human cell lines that maintain their telomeres using the ALT mechanism, the IIICF/c line has telomeres of very heterogeneous length (Rogan et al, 1995) and forms APBs (Jiang et al, 2005). IIICF/c cells were used in our recent study, which demonstrated a close link between the formation of APBs and ALT activity (Jiang et al, 2005).…”

“…The spontaneously immortalized Li-Fraumeni syndrome fibroblast line IIICF/c (Rogan et al, 1995), SV40-immortalized human fibroblasts GM847DM (from Dr O PereiraSmith) and GM00639 (Coriell), hTERT-immortalized human fibroblasts JFCF-6/hTERT/3 (Z Zhong et al, unpublished) and IMR90 primary fibroblasts (American-type culture collection (ATCC)) were cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) and 50 mg/ml gentamicin in a 5% CO 2 -humidified atmosphere at 371C.…”

“…Although this occurred in several ALT cell lines that were tested, we chose IIICF/c cells for development of the assay system because this is the cell line for which the most compelling data regarding linkage between ALT activity and the ability to form APBs exists (Jiang et al, 2005). By all parameters tested, IIICF/c is a typical ALT cell line exhibiting the characteristically heterogeneous telomere length pattern (Rogan et al, 1995), APBs (Yeager et al, 1999), rapid fluctuation of telomere length (Jiang et al, 2005) and circular extrachromosomal telomeric repeat DNA (Fasching CL, Jiang W-Q and Reddel RR, unpublished data).…”

Li-Fraumeni syndrome – a molecular and clinical review

“…However Li-Fraumeni fibroblasts that are maintained in culture and not subjected to any damaging agents also show a range of abnormalities. As they are cultured through progressive population doublings, they show an increased number of chromosome abnormalities of all types Yin et al, 1992;Rogan et al, 1995), loss of the wild-type allele (Yin et al, 1992;Rogan et al, 1995), changes in morphology and, rarely, spontaneous immortalization Rogan et al, 1995) accompanied by telomere elongation (Rogan et al, 1995). Spontaneous immortalization has also been reported in breast epithelial cells from a LFS patient with a germline TP53 mutation (Shay et al, 1995), and even Li-Fraumeni cells that fail to immortalize spontaneously can be induced to do so by treatment with various agents that have no effect on normal cells (Shay et al, 1995;Tsutsui et al, 1995).…”