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G A Currie

Publications and source records attributed to G A Currie.

66 records · Page 4Linked to original sources
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A novel transforming gene in a human malignant melanoma cell line.

Cellular transforming genes can be detected in human tumours by DNA-mediated transfection into NIH 3T3 mouse fibroblasts. The activated transforming genes have been, in most cases, members of the ras gene family, of which the most frequently found is the c-Ki-ras oncogene and least frequently the c-Ha-ras gene. An increasing number of studies has identified the presence of activated N-ras (which has no known viral homologue) in human tumour cell lines. Furthermore, other transforming genes, distinct from the ras gene family, have been reported in B-and T-cell lymphomas. The activation of c-Ha-ras and N-ras has been described in some cell lines derived from cases of human malignant melanoma. Here we describe the presence of transforming activity in the DNA from a human melanoma cell line which shows weak homology with members of the ras oncogene family.

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Cellular immortalization by a cDNA clone encoding the transformation-associated phosphoprotein p53.

Malignant transformation of primary cells requires at least two distinct and characteristic alterations in cellular behaviour. The first, cellular immortality, can be induced by chemical carcinogens or by cloned oncogenes such as polyoma large T (ref. 4), adenovirus early region 1A (E1A) or the oncogene from avian (MC29) myelocytomatosis virus, v-myc. Cells whose in vitro life-span has been extended by these procedures can be fully transformed by transfection with oncogenes belonging to a different complementation group, including genes of the ras family, adenovirus E1b and polyoma virus middle T (refs 4, 5). The unstable cellular phosphoprotein p53 is frequently present at elevated levels in transformed cells and is stabilized by the formation of complexes with simian virus 40 (SV40) large T or adenovirus E1b 57K protein. Although several reports have associated p53 with cell proliferation, its role remains obscure. We have cloned complementary DNA sequences encoding murine p53 and report here that transfection of p53 expression constructs into cells of finite lifespan in vitro results in cellular immortality and susceptibility to transformation by a ras oncogene.

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The cellular oncogene p53 can be activated by mutagenesis.

P53 is a cellular phosphoprotein of short half-life (t1/2) which is present at elevated levels in cells transformed by various stimuli including viruses, chemicals and radiation. p53 forms specific stable complexes with simian virus 40 (SV40) large-T antigen and an adenovirus E1b protein of relative molecular mass (Mr) 57,000. A number of reports have associated p53 with cell proliferation, and p53 complementary DNA expression constructs immortalize primary cells in vitro and render them sensitive to transformation by an activated ras oncogene. We have examined the biological properties of a set of p53 expression constructs, and report here that cellular immortalization by a wild-type p53 cDNA gene is conditional upon the promoter/enhancer construction used, but that p53 can extend cellular lifespan by a second distinct mechanism involving rearrangements of the coding sequence which give rise to stable protein products. Cells immortalized by one of these mutants are refractory to subsequent transformation by a ras oncogene, indicating that cellular immortalization and ras cooperation are separate activities.

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The strategic role of health informatics in integrated delivery systems.

Having accurate measures and high-quality health information is critically important for all providers today. Integrated delivery systems are faced with increasing demands for numerous redundant, sometimes conflicting, performance measurement and reporting data from managed care customers, regulators, and accreditors. When implemented independently within each organizational subunit, these measurement systems are costly and difficult to manage. Centralization of all measurement services can maximize the productivity of the costly resources required to deliver them and can achieve efficiencies, cost savings, and a better balance between internal and external resources while collecting information that is of a higher quality for managerial and clinical decision making.

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