PMID- 7565779
OWN - NLM
STAT- MEDLINE
DCOM- 19951121
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 15
IP  - 11
DP  - 1995 Nov
TI  - Role of EGR-1 in thapsigargin-inducible apoptosis in the melanoma cell line 
      A375-C6.
PG  - 6262-72
AB  - Induction of apoptosis by diverse exogenous signals is dependent on elevation of 
      intracellular Ca2+. This process of cell death can be blocked by actinomycin D, 
      indicating that it requires gene transcription events. To identify genes that are 
      required for apoptosis, we used thapsigargin (TG), which inhibits endoplasmic 
      reticulum-dependent Ca(2+)-ATPase and thereby increases cytosolic Ca2+. Exposure 
      to TG led to induction of the zinc finger transcription factor, EGR-1, and 
      apoptosis in human melanoma cells, A375-C6. To determine the functional relevance 
      of EGR-1 expression in TG-inducible apoptosis, we employed a dominant negative 
      mutant which functionally competes with EGR-1 in these cells. Interestingly, the 
      dominant negative mutant inhibited TG-inducible apoptosis. Consistent with this 
      observation, an antisense oligomer directed against Egr-1 also led to a 
      diminution of the number of cells that undergo TG-inducible apoptosis. These 
      results suggest a novel regulatory role for EGR-1 in mediating apoptosis that is 
      induced by intracellular Ca2+ elevation. We have previously shown that in these 
      melanoma cells, EGR-1 acts to inhibit the growth arresting action of 
      interleukin-1. Together, these results imply that EGR-1 plays inducer-specific 
      roles in growth control.
FAU - Muthukkumar, S
AU  - Muthukkumar S
AD  - Department of Surgery, University of Kentucky, Lexington 40536, USA.
FAU - Nair, P
AU  - Nair P
FAU - Sells, S F
AU  - Sells SF
FAU - Maddiwar, N G
AU  - Maddiwar NG
FAU - Jacob, R J
AU  - Jacob RJ
FAU - Rangnekar, V M
AU  - Rangnekar VM
LA  - eng
GR  - CA52837/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Terpenes)
RN  - 0 (Transcription Factors)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Apoptosis
MH  - Base Sequence
MH  - Calcium/*physiology
MH  - Calcium-Transporting ATPases/*antagonists & inhibitors
MH  - DNA-Binding Proteins/*physiology
MH  - Early Growth Response Protein 1
MH  - Endoplasmic Reticulum/enzymology
MH  - Enzyme Inhibitors/*pharmacology
MH  - *Genes, Immediate-Early
MH  - Genes, Wilms Tumor
MH  - Humans
MH  - *Immediate-Early Proteins
MH  - Melanoma
MH  - Molecular Sequence Data
MH  - Oligonucleotides, Antisense/chemistry
MH  - Terpenes/*pharmacology
MH  - Thapsigargin
MH  - Transcription Factors/*physiology
MH  - Tumor Cells, Cultured
PMC - PMC230878
EDAT- 1995/11/01 00:00
MHDA- 1995/11/01 00:01
PMCR- 1995/11/01
CRDT- 1995/11/01 00:00
PHST- 1995/11/01 00:00 [pubmed]
PHST- 1995/11/01 00:01 [medline]
PHST- 1995/11/01 00:00 [entrez]
PHST- 1995/11/01 00:00 [pmc-release]
AID - 10.1128/MCB.15.11.6262 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1995 Nov;15(11):6262-72. doi: 10.1128/MCB.15.11.6262.