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

Abstract

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.

Authors:
; ; ; ; ; ; ;  [1]
  1. Los Alamos National Lab., NM (United States)
Publication Date:
OSTI Identifier:
6831618
Report Number(s):
CONF-9303114-
Journal ID: ISSN 0196-4763; CODEN: CYTODQ
Resource Type:
Conference
Journal Name:
Cytometry (Baltimore); (United States)
Additional Journal Information:
Journal Volume: 6; Conference: 16. congress of the International Society for Analytical Cytology, Colorado Springs, CO (United States), 21-26 Mar 1993; Journal ID: ISSN 0196-4763
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Crissman, H A, Gadbois, D M, Tobey, R A, Stevenson, A P, Kraemer, P M, Bustos, L D, Dickson, J A, and Bradbury, E M. Differences in kinase-mediated regulation of cell cycle progression in normal and transformed cells. United States: N. p., 1993. Web.
Crissman, H A, Gadbois, D M, Tobey, R A, Stevenson, A P, Kraemer, P M, Bustos, L D, Dickson, J A, & Bradbury, E M. Differences in kinase-mediated regulation of cell cycle progression in normal and transformed cells. United States.
Crissman, H A, Gadbois, D M, Tobey, R A, Stevenson, A P, Kraemer, P M, Bustos, L D, Dickson, J A, and Bradbury, E M. 1993. "Differences in kinase-mediated regulation of cell cycle progression in normal and transformed cells". United States.
@article{osti_6831618,
title = {Differences in kinase-mediated regulation of cell cycle progression in normal and transformed cells},
author = {Crissman, H A and Gadbois, D M and Tobey, R A and Stevenson, A P and Kraemer, P M and Bustos, L D and Dickson, J A and Bradbury, E M},
abstractNote = {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.},
doi = {},
url = {https://www.osti.gov/biblio/6831618}, journal = {Cytometry (Baltimore); (United States)},
issn = {0196-4763},
number = ,
volume = 6,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 1993},
month = {Fri Jan 01 00:00:00 EST 1993}
}

Conference:
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