PMID- 9419976
OWN - NLM
STAT- MEDLINE
DCOM- 19980112
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 15
IP  - 23
DP  - 1997 Dec 4
TI  - Bcl-2 inhibits c-fos induction by calcium.
PG  - 2849-53
AB  - Transient elevation of cytosolic Ca2+ induces the expression of a variety of 
      genes involved in cell growth and transformation, including the early response 
      gene c-fos. Previously, we reported that Bcl-2 inhibits the transient elevation 
      of cytosolic Ca2+ induced by thapsigargin (TG), a selective inhibitor of the 
      endoplasmic reticulum-associated Ca2+-ATPase. Therefore, to determine if the 
      effect of Bcl-2 on cytosolic Ca2+ elevation modulates Ca2+ signaling, we 
      investigated the induction of c-fos by TG in WEHI7.2 mouse lymphoma cells, 
      control transfectants (WEHI7.2-neo), and transfectants that stably express a high 
      level of Bcl-2 (W.Hb12 and W.Hb15). TG induced 20-fold elevation of c-fos mRNA in 
      WEHI7.2 and WEHI7.2-neo cells, but c-fos mRNA induction by TG was only fivefold 
      in W.Hb12 and W.Hb15 cells. In contrast, phorbol 12-myristate acetate induced 
      marked c-fos mRNA elevation in both WEHI7.2 and W.Hb12 cells, indicating that the 
      inhibitory effect of Bcl-2 is selective for induction of c-fos by Ca2+. To 
      measure c-fos promoter activity, WEHI7.2 and W.Hb12 cells were transiently 
      transfected with a c-fos promoter-luciferase reporter plasmid. TG induced c-fos 
      promoter activity in WEHI7.2 cells, but not in W.Hb12 cells. In WEHI7.2 cells, 
      the signal for c-fos induction by TG was cytosolic Ca2+ elevation, as the 
      increase in both c-fos mRNA level and promoter activity were prevented by 
      lowering extracellular Ca2+ concentration, a condition that inhibits cytosolic 
      Ca2+ elevation by reducing the TG-mobilizable Ca2+ pool. In summary, the findings 
      indicate that Bcl-2 regulates Ca2+ signaling.
FAU - Qi, X M
AU  - Qi XM
AD  - Department of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, 
      USA.
FAU - Simonson, M
AU  - Simonson M
FAU - Distelhorst, C W
AU  - Distelhorst CW
LA  - eng
GR  - R01 CA42755-11/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 67526-95-8 (Thapsigargin)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*antagonists & inhibitors/*physiology
MH  - Cytosol/metabolism/physiology
MH  - Extracellular Space/metabolism/physiology
MH  - *Gene Expression Regulation, Neoplastic/drug effects
MH  - *Genes, fos/drug effects
MH  - Lymphoma
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Promoter Regions, Genetic/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/*physiology
MH  - Signal Transduction/drug effects/*genetics
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Thapsigargin/pharmacology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1998/01/07 00:00
MHDA- 1998/01/07 00:01
CRDT- 1998/01/07 00:00
PHST- 1998/01/07 00:00 [pubmed]
PHST- 1998/01/07 00:01 [medline]
PHST- 1998/01/07 00:00 [entrez]
AID - 10.1038/sj.onc.1201463 [doi]
PST - ppublish
SO  - Oncogene. 1997 Dec 4;15(23):2849-53. doi: 10.1038/sj.onc.1201463.