Differences in kinase-mediated regulation of cell cycle progression in normal and transformed cells

Conference · Fri Jan 01 00:00:00 EST 1993 · Cytometry (Baltimore); (United States)

OSTI ID:6831618

Crissman, H A; Gadbois, D M; Tobey, R A; Stevenson, A P; Kraemer, P M; Bustos, L D; Dickson, J A; Bradbury, E M ^[1]

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1. Los Alamos National Lab., NM (United States)

Staurosporine (Stsp), a general protein kinase inhibitor, was used to investigate the role of kinase-mediated mechanisms in regulating mammalian cell proliferation. Low levels of Stsp (1-2nM) prevented nontransformed cells from entering S phase, indicating that protein phosphorylation processes are essential for commitment of DNA replication in normal cells. Cells resumed cycling when Stsp was removed. The period of sensitivity of nontransformed human diploid fibroblasts to low levels of the drug commenced 3 h later than the G0/G1 boundary and extended through the G1/S boundary. The initial block point at 3 h corresponds neither to the serum nor the amino acid restriction point. In contrast, neither low nor high concentrations (100nm) of Stsp affected G1 progression of transformed cells. High drug concentrations blocked normal cells in G1 and G2 but affected only G2-progression in transformed cells. These results indicate that kinase-mediated regulation of DNA replication is lost as a result of neoplastic transformation, but the G2-arrest mechanism remains intact.

• OSTI ID: 6831618
• Report Number(s): CONF-9303114-; CODEN: CYTODQ
• Journal Information: Cytometry (Baltimore); (United States), Vol. 6; Conference: 16. congress of the International Society for Analytical Cytology, Colorado Springs, CO (United States), 21-26 Mar 1993; ISSN 0196-4763
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CELL PROLIFERATION
CONTROL
PHOSPHOTRANSFERASES
QUANTITY RATIO
DNA REPLICATION
ENZYME INHIBITORS
ONCOGENIC TRANSFORMATIONS
CELL TRANSFORMATIONS
ENZYMES
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
PROTEINS
TRANSFERASES
550300* - Cytology
550200 - Biochemistry