Human diploid cells derived from normal tissue undergo a characteristic pattern of growth in cell culture, ending with a non-replicative phase and, finally, cell death. Models of cellular aging have been developed which suggest analogy between this pattern and behavior of the organism in vivo; hence, the term """"""""senescence"""""""". Human diploid fibroblasts (HF) which had been infected in vitro by the oncogenic DNA virus SV40 have been found to overcome this phenomenon. We have found that a clonal isolate of a HF transformed by an origin-defective mutant of SV40 (SVori-) with an intact early region permits isolation of immortalized cells at an unusually high frequency. Analysis of several such immortalized HF from individual cloned transformants will be performed to identify possible common genetic alterations. Further, we propose to study a series of independent HF transformed by origin-defective mutants of SV40 with a temperature-sensitive T antigen (ts A mutants) to assess possible bases for the role of SV40 in the initiation and maintenance of a continuous cell strain.

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National Institute on Aging (NIA)
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University of Medicine & Dentistry of NJ
Schools of Dentistry
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Yan, Ling; Bowman, Marion A Hofmann (2014) Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100/RAGE and FGF23. Inflamm Cell Signal 1:
Parrott, Andrew M; Tsai, Michael; Batchu, Priyanka et al. (2011) The evolution and expression of the snaR family of small non-coding RNAs. Nucleic Acids Res 39:1485-500
Banga, S S; Peng, L; Dasgupta, T et al. (2009) PHF10 is required for cell proliferation in normal and SV40-immortalized human fibroblast cells. Cytogenet Genome Res 126:227-42
Sahay, S; Pannucci, N L; Mahon, G M et al. (2008) The RhoGEF domain of p210 Bcr-Abl activates RhoA and is required for transformation. Oncogene 27:2064-71
Olabisi, Oyenike O; Mahon, Gwendolyn M; Kostenko, Elena V et al. (2006) Bcr interacts with components of the endosomal sorting complex required for transport-I and is required for epidermal growth factor receptor turnover. Cancer Res 66:6250-7
Harvey, Bohdan P; Banga, Satnam S; Ozer, Harvey L (2004) Regulation of the multifunctional Ca2+/calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts. J Biol Chem 279:24889-98
Macera-Bloch, Lisa; Houghton, JeanMarie; Lenahan, Melanie et al. (2002) Termination of lifespan of SV40-transformed human fibroblasts in crisis is due to apoptosis. J Cell Physiol 190:332-44
Benanti, Jennifer A; Williams, Dawnnica K; Robinson, Kristin L et al. (2002) Induction of extracellular matrix-remodeling genes by the senescence-associated protein APA-1. Mol Cell Biol 22:7385-97
Tevethia, M J; Ozer, H L (2001) SV40-mediated immortalization. Methods Mol Biol 165:185-99
Ozer, H L (2000) SV40-mediated immortalization. Prog Mol Subcell Biol 24:121-53

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