Journal ArticleDOI
Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts.
Tara. Seshadri,Judith Campisi +1 more
TLDR
The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c-fos; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.Abstract:
Normal cells in culture invariably undergo senescence, whereby they cease proliferation after a finite number of doublings. Irreversible changes in gene expression occurred in senescent human fetal lung fibroblasts: a non-cell cycle-regulated mRNA was partially repressed; an unusual polyadenylated histone mRNA was expressed; although serum induced c-H-ras, c-myc, and ornithine decarboxylase mRNA normally, ornithine decarboxylase activity was deficient; and serum did not induce mRNA for a replication-dependent histone and for the c-fos proto-oncogene. The loss of c-fos inducibility was the result of a specific, transcriptional block. The results suggest that senescent fibroblasts were unable to proliferate because of, at least in part, selective repression of c-fos; moreover, the multiple changes in gene expression support the view that cellular senescence is a process of terminal differentiation.read more
Citations
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
Journal ArticleDOI
Cellular senescence: when bad things happen to good cells
TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
Journal ArticleDOI
Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging.
TL;DR: It is shown that senescent human fibroblasts stimulate premalignant and malignant, but not normal, epithelial cells to proliferate in culture and form tumors in mice, suggesting it is an example of evolutionary antagonistic pleiotropy.
BookDOI
The Cell Cycle
TL;DR: It is shown that the presence of phosphatase inhibitors can have major effects on the levels of phosphorylation and the activities of the kinase extracted from cells, and the combination of okadaic acid and sodium vanadate was most effective in protecting p34cdc2 against cellular phosphatases.
Journal ArticleDOI
Oxidative stress and gene regulation.
R.G Allen,Maria Tresini +1 more
TL;DR: The discussion presented here provides a tabular summary of many of the redox effects on gene expression and signaling pathways that are currently known to exist, and highlights the growing number of pathways shown to be dependent on oxidation or antioxidation.
References
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Journal ArticleDOI
The limited in vitro lifetime of human diploid cell strains
TL;DR: The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established.
Journal ArticleDOI
Induction of c- fos gene and protein by growth factors precedes activation of c- myc
TL;DR: Stimulation of fibroblasts with serum or purified growth factors leads to a dramatic induction of expression of both c-fos mRNA and protein within a few minutes, followed by activation of c-myc.
Journal Article
Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype.
Journal ArticleDOI
Requirement for ras proto-oncogene function during serum-stimulated growth of NIH 3T3 cells.
TL;DR: It is reported here that NIH 3T3 cells induced to divide by adding serum to the culture medium are unable to enter the S phase of the cell cycle after microinjection of anti-ras antibody, showing that the protein product of the ras proto-oncogene is required for initiation of the S-phase in NIH 3 T3 cells.
Journal ArticleDOI
A c-myc antisense oligodeoxynucleotide inhibits entry into S phase but not progress from G0 to G1
Reino Heikkila,Gisela Schwab,Eric Wickstrom,Shee Loong Loke,Dov H. Pluznik,Rosemary Watt,Leonard M. Neckers +6 more
TL;DR: Exogenous addition to bulk cell cultures of small antisense oligomers inhibits mitogen-induced c-myc protein expression in human T lymphocytes and prevents S phase entry and Interestingly, c- myc antisense treatment did not inhibit G0 to G1 traversal as assessed by morphologic blast transformation, transcriptional activation of the IL-2R and TfR genes, or induction of 3H-uridine incorporation.