PMID- 12040020
OWN - NLM
STAT- MEDLINE
DCOM- 20030110
LR  - 20161124
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 16
IP  - 6
DP  - 2002 Jun
TI  - Activity of the GR in G2 and mitosis.
PG  - 1352-66
AB  - To elucidate the mechanisms mediating the reported transient physiological 
      glucocorticoid resistance in G2/M cell cycle phase, we sought to establish a 
      model system of glucocorticoid-resistant cells in G2. We synchronized various 
      cell lines in G2 to measure dexamethasone (DEX)-induced transactivation of either 
      two endogenous promoters (rat tyrosine aminotransferase and mouse metallothionein 
      I) or the mouse mammary tumor virus (MMTV) promoter stably or transiently 
      transfected. To circumvent the need for synchronization drugs, we stably 
      transfected an MMTV-driven green fluorescent protein to directly correlate 
      DEX-induced transactivation with the cell cycle position for each cell of an 
      asynchronous population using flow cytometry. Surprisingly, all promoters tested 
      were DEX-inducible in G2. Even in mitotic cells, only the stably transfected MMTV 
      promoter was repressed, whereas the same promoter transiently transfected was 
      inducible. The use of Hoechst 33342 for synchronization in previous studies 
      probably caused a misinterpretation, because we detected interference of this 
      drug with GR-dependent transcription independent of the cell cycle. Finally, GR 
      activated a simple promoter in G2, excluding a functional effect of cell 
      cycle-dependent phosphorylation of GR, as implied previously. We conclude that GR 
      itself is fully functional throughout the entire cell cycle, but GR 
      responsiveness is repressed in mitosis due to chromatin condensation rather than 
      to specific modification of GR.
FAU - Abel, G Alexander
AU  - Abel GA
AD  - Max Planck Institute of Psychiatry, Munich D-80804, Germany.
FAU - Wochnik, Gabriela M
AU  - Wochnik GM
FAU - Ruegg, Joelle
AU  - Ruegg J
FAU - Rouyer, Audrey
AU  - Rouyer A
FAU - Holsboer, Florian
AU  - Holsboer F
FAU - Rein, Theo
AU  - Rein T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Benzimidazoles)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.6.1.5 (Tyrosine Transaminase)
RN  - P976261J69 (bisbenzimide ethoxide trihydrochloride)
SB  - IM
MH  - Animals
MH  - Benzimidazoles/pharmacology
MH  - CHO Cells
MH  - Cell Line
MH  - Cricetinae
MH  - Dexamethasone/pharmacology
MH  - Enzyme Induction/drug effects
MH  - Flow Cytometry
MH  - *G2 Phase
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - *Mitosis
MH  - Promoter Regions, Genetic/genetics
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Templates, Genetic
MH  - Transcriptional Activation/drug effects
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tyrosine Transaminase/genetics/metabolism
EDAT- 2002/06/01 10:00
MHDA- 2003/01/11 04:00
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2003/01/11 04:00 [medline]
PHST- 2002/06/01 10:00 [entrez]
AID - 10.1210/mend.16.6.0842 [doi]
PST - ppublish
SO  - Mol Endocrinol. 2002 Jun;16(6):1352-66. doi: 10.1210/mend.16.6.0842.