Changes in cell shape and anchorage in relation to the restriction point.
The restriction point (R) separates the G1 phase of continuously cycling cells into two functionally different parts. The first part, G1-pm, represents the growth factor dependent post-mitotic interval from mitosis to R, which is of constant length (3-4 h). The second part, G1-ps, represents the growth factor independent, pre-S phase interval of G1 that lasts from R to S and that varies in time from 1 to 10 h. G1-pm cells rapidly exit (within 1 h) from the cell cycle and enter G0 as a response to serum withdrawal. The finding that R occurs at a set time after mitosis indicates that R may be related to the metabolic and/or structural changes that the cell underwent during the previous mitosis. We have recently shown that phosphorylation of the retinoblastoma tumor suppressor protein (pRb) is not the molecular mechanism behind R, as has been suggested previously. Here, we present an alternative explanation for R. In the present study, we applied a single cell approach using time-lapse analysis, which revealed that upon serum starvation the G1-pm cells rapidly underwent a transient change in cell shape from flat to spherical before exiting to G0. Platelet derived growth factor (PDGF) counteracted this change in shape and also prevented exit to G0 to the same extent. Furthermore epidermal growth factor (EGF) and insulin like growth factor (IGF-1), which only partially counteracted this change, only partially counteracts exit to G0. These data clearly indicate a direct link between change in cell shape and exit to G0 in G1-cells that have not passed R.
Martinsson
Hanna-Stina
HS
Karolinska Institutet, Department of Oncology-Pathology, Karolinska Hospital/CCK R8:04, Stockholm, Sweden.
Zickert
Peter
P
Starborg
Maria
M
Larsson
Olle
O
Zetterberg
Anders
A
D016475:3T3 Cells; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D000077214:Becaplermin; D001798:Blood Proteins / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis
D000925:Anticoagulants; D001798:Blood Proteins; D016895:Culture Media, Serum-Free; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin