Replicative Potential Of Cells Research Articles

Roles of eEF-2 kinase in cancer.

To provide a summary of the relationship between the eEF-2/eEF-2 kinase pathway and each phase of malignant neoplasms. The speci?c importance of this relationship in understanding and treating cancer was also explored. The data used in this review were mainly obtained from the articles listed in HighWire and PubMed in English. The search terms were "eEF-2 kinase", "oncogenesis", and "tumor progression". This review relates the observation that the overexpression of eEF-2 kinase is seen in cancer, and highlights that it has emerged as promoting the development of many malignant phenotypes when unregulated. This includes increasing the replicative potential of cells, angiogenesis, invasion and metastasis, and evasion of apoptosis. eEF-2 kinase is a structurally and functionally unique protein kinase. The increased activity of this protein in cancer cells is a protective mechanism to allow tumor growth and evolution, and resist cell death through the eEF-2/eEF-2 kinase pathway, but it also makes a potential target for therapy. eEF-2 kinase fills critical niches in the life of a cancer cell and the eEF-2/eEF-2 kinase pathway is a key biochemical sensor.

Effects of insulin-like growth factor i on the regulation of telomere length and telomerase activity in cord blood t cells

Insulin-like growth factor-I (IGF-I) has been shown to enhance the PHA-induced increase in telomerase activity for cord blood (CB) mononuclear cells. It is hypothesized that the IGF-I on telomerase activity may have an impact on the telomere length and replicative potential of cells. In this study, we have cultured isolate CB T cells (CD3+ purity = 98%) in a similar serum free liquid medium containing: (a) NoGF; (b) IGF-I, (c) PHA, and (d) IGF-I + PHA. The telomere length of cells harvested on Day 0, 3, 5, 8, 14 and 21 was measured by a quantitative flow cytometry based fluorescence in situ hybridisation technique (Q-Flow FISH). The corresponding telomerase activity was determined by the non-radioactive PCR-based Telomeric Repeat Amplification Protocol (TRAP). The telomere length of PHA stimulated T cells increased to a peak level on Day 8 and decreased back to the initial level by Day 21. The addition of IGF-1 increased the telomere length of PHA stimulated T cells throughout the course of the culture. Interestingly, this later increase in telomere length was not accompanied by a high level of telomerase in the cells at later time points in the culture. The heterogeneous relationship between telomerase and telomere length suggested that the effect of IGF-I on telomere length elongation may be due to the involvement of alternative pathways other than the initial enhancement in telomerase activity in the cells. Further experiments are needed to clarify the mechanisms involved and the impact on replicative potential of cells. This data may be useful for the ex vivo expansion of T cells for adoptive immunotherapy and transplantation.

THE ANTIPROLIFERATIVE ASPECTS OF MORTALIN (REVIEW)

Cellular mortal and immortal phenotypes as defined by the limited and the infinite capacity of cells to divide are the characteristics of normal and cancerous cells in culture. Numerous strategies that have been employed to understand the mechanism(s) of normal as well as tumor cell growth have revealed that these are genetically controlled, however, the genes and the synchronized regulations remain largely undefined so far. The present report reviews the identification of mortalin, a novel member of murine hsp70 family of proteins, as a gene involved in pathways that determine divisional phenotype of cells in vitro. In the present study, the anti-proliferative activity of mortalin is demonstrated also in human skin fibroblasts (TIG-73PD) by microinjection of anti-mortalin antibody. Furthermore, studies on the mortalin immunofluorescence patterns in SV40-immortalized pre-crisis and post-crisis human cells have revealed that the change in the intracellular distribution of mortalin is linked to the change in the divisional phenotype of cells. Thus, the studies to resolve the molecular basis of association of the cytosolically distributed form of mortalin with cellular mortal phenotype would be important in understanding of the mechanism(s) that determine replicative potential of cells in culture.