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Growth factors induce early pre‐replicative changes in senescent human fibroblasts.
Author(s) -
Paulsson Y.,
Bywater M.,
PfeiferOhlsson S.,
Ohlsson R.,
Nilsson S.,
Heldin C.H.,
Westermark B.,
Betsholtz C.
Publication year - 1986
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1986.tb04479.x
Subject(s) - biology , platelet derived growth factor receptor , platelet derived growth factor , autophosphorylation , microbiology and biotechnology , cell cycle , growth factor , cell growth , cell culture , receptor , cell , phosphorylation , genetics , protein kinase a
As human fibroblasts in culture senesce their response to platelet‐derived growth factor (PDGF) becomes attenuated. To clarify at which level such cells are blocked in the pre‐replicative part of the cell cycle, we have analysed PDGF‐induced pre‐replicative events in senescent (phase III) cultures. We found that phase III cells retain a normal number of PDGF receptors and that these are functional with regard to PDGF‐induced receptor autophosphorylation. Phase III cells also respond to PDGF by rapid actin reorganization and increased levels of c‐fos and c‐myc mRNA, similar to growth‐arrested phase II fibroblasts. However, the expression of the nuclear antigen K‐67, which in phase II cell is induced in S‐phase and continues to be expressed throughout the cell cycle, is not induced in phase III cells in response to PDGF. We conclude that phase III human fibroblasts, although blocked with regard to proliferation, still retain a functional growth factor receptor system, and display early responses when exposed to growth factors, such as changes in the cytoskeleton and the expression of proto‐oncogenes.