ATP inhibition of proliferation of immortalized human fibroblasts is greater than that of normal human diploid fibroblasts.

1998 ◽  
Author(s):  
B Katayama ◽  
M Sakaguchi ◽  
J W Li ◽  
H Pu ◽  
Y Inoue ◽  
...  
Keyword(s):  
Human Fibroblasts ◽  
Inhibition Of Proliferation ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Atp Inhibition ◽  
Normal Human

Altered chromosome 6 in immortal human fibroblasts

1992 ◽  
Vol 12 (5) ◽  
pp. 2273-2281
Author(s):  
K Hubbard-Smith ◽  
P Patsalis ◽  
J R Pardinas ◽  
K K Jha ◽  
A S Henderson ◽  
...  
Keyword(s):  
Cell Lines ◽  
Human Fibroblasts ◽  
Rare Event ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Chromosome 6 ◽  
Karyotypic Analysis ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Immortal Cells

Human diploid fibroblasts have a limited life span in vitro, and spontaneous immortalization is an extremely rare event. We have used transformation of human diploid fibroblasts by an origin-defective simian virus 40 genome to develop series of genetically matched immortal cell lines to analyze immortalization. Comparison of a preimmortal transformant (SVtsA/HF-A) with its uncloned and cloned immortalized derivatives (AR5 and HAL) has failed to reveal any major alteration involving the simian virus 40 genome. Karyotypic analysis, however, demonstrated that all of the immortal cell lines in this series have alterations of chromosome 6 involving loss of the portion distal to 6q21. The karyotypic analysis was corroborated by DNA analyses. Southern analysis demonstrated that only one copy of three proto-oncogene loci (ros1, c-myb, and mas1) on 6q was retained in immortal cells. Polymerase chain reaction analysis of the microsatellite polymorphism at 6q22 (D6S87) showed loss of heterozygosity. In addition, elevated expression of c-myb (6q22-23) was observed. We hypothesize that the region at and/or distal to 6q21 plays a role in immortalization, consistent with the presence of a growth suppressor gene.

scholarly journals Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and theTumor Suppressors p16INK4a andp53

2004 ◽  
Vol 24 (4) ◽  
pp. 1540-1559 ◽  
Author(s):  
Linda A. Scott ◽  
J. Keith Vass ◽  
E. Kenneth Parkinson ◽  
David A. F. Gillespie ◽  
Joseph N. Winnie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Human Cancer ◽  
Human Fibroblasts ◽  
Growth Factor Receptor ◽  
Dysplastic Lesion ◽  
Human Diploid Fibroblasts ◽  
Affymetrix Genechips ◽  
Late Event ◽  
Normal Human

ABSTRACT Invasion is generally perceived to be a late event during the progression of human cancer, but to date there are no consistent reports of alterations specifically associated with malignant conversion. We provide evidence that the v-Fos oncogene induces changes in gene expression that render noninvasive normal human diploid fibroblasts highly invasive, without inducing changes in growth factor requirements or anchorage dependence for proliferation. Furthermore, v-Fos-stimulated invasion is independent of the pRb/p16INK4a and p53 tumor suppressor pathways and telomerase. We have performed microarray analysis using Affymetrix GeneChips, and the gene expression profile of v-Fos transformed cells supports its role in the regulation of invasion, independent from proliferation. We also demonstrate that invasion, but not proliferation, is dependent on the activity of the up-regulated epidermal growth factor receptor. Taken together, these results indicate that AP-1-directed invasion could precede deregulated proliferation during tumorigenesis and that sustained activation of AP-1 could be the epigenetic event required for conversion of a benign tumor into a malignant one, thereby explaining why many malignant human tumors present without an obvious premalignant hyperproliferative dysplastic lesion.

scholarly journals Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts.

1989 ◽  
Vol 9 (7) ◽  
pp. 3088-3092 ◽  
Author(s):  
W E Wright ◽  
O M Pereira-Smith ◽  
J W Shay
Keyword(s):  
Cellular Senescence ◽  
Rare Event ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
T Antigen ◽  
Diploid Fibroblasts ◽  
Human Diploid Fibroblasts ◽  
Normal Human ◽  
Immortal Cells ◽  
Cellular Dna

IMR-90 normal human diploid fibroblasts, transfected with a steroid inducible mouse mammary tumor virus-driven simian virus 40 T antigen, were carried through crisis to yield an immortal cell line. Growth was dependent on the presence of the inducer (dexamethasone) during both the extended precrisis life span of the cells and after immortalization. After dexamethasone removal, immortal cells divided once or twice and then accumulated in G1. These results are best explained by a two-stage model for cellular senescence. Mortality stage 1 (M1) causes a loss of mitogen responsiveness and arrest near the G1/S interface and can be bypassed or overcome by the cellular DNA synthesis-stimulating activity of T antigen. Mortality stage 2 (M2) is an independent mechanism that is responsible for the failure of cell division during crisis. The inactivation of M2 is a rare event, probably of mutational origin in human cells, independent of or only indirectly related to the expression of T antigen. Under this hypothesis, T-antigen-immortalized cells contain an active but bypassed M1 mechanism and an inactivated M2 mechanism. These cells are dependent on the continued expression of T antigen for the maintenance of immortality for the same reason that precrisis cells are dependent on T antigen for growth: both contain an active M1 mechanism.

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