PMID- 12743373
OWN - NLM
STAT- MEDLINE
DCOM- 20030716
LR  - 20181113
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 100
IP  - 11
DP  - 2003 May 27
TI  - Inhibition of p53-induced apoptosis without affecting expression of p53-regulated 
      genes.
PG  - 6718-23
AB  - Using DNA microarray and clustering of expressed genes we have analyzed the 
      mechanism of inhibition of wild-type p53-induced apoptosis by the cytokine 
      interleukin 6 (IL-6) and the calcium mobilizer thapsigargin (TG). Clustering 
      analysis of 1,786 genes, the expression level of which changed after activation 
      of wild-type p53 in the absence or presence of IL-6 or TG, showed that these 
      compounds did not cause a general inhibition of the ability of p53 to up-regulate 
      or down-regulate gene expression. Expression of various p53 targets implicated as 
      mediators of p53-induced apoptosis was also not affected by IL-6 or TG. These 
      compounds thus can bypass the effect of wild-type p53 on gene expression and 
      inhibit apoptosis. IL-6 and TG activated different p53-independent pathways of 
      gene expression that include up-regulation of antiapoptotic genes. IL-6 and TG 
      also activated different differentiation-associated genes. The ability of 
      compounds such as cytokines and calcium mobilizers to inhibit p53-mediated 
      apoptosis without generally inhibiting gene expression regulated by p53 can 
      facilitate tumor development and tumor resistance to radiation and chemotherapy 
      in cells that retain wild-type p53.
FAU - Lotem, Joseph
AU  - Lotem J
AD  - Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, 
      Israel.
FAU - Gal, Hilah
AU  - Gal H
FAU - Kama, Rachel
AU  - Kama R
FAU - Amariglio, Ninette
AU  - Amariglio N
FAU - Rechavi, Gideon
AU  - Rechavi G
FAU - Domany, Eytan
AU  - Domany E
FAU - Sachs, Leo
AU  - Sachs L
FAU - Givol, David
AU  - Givol D
LA  - eng
SI  - GENBANK/AF067774
SI  - RefSeq/NM_009735
GR  - P01 CA065930/CA/NCI NIH HHS/United States
GR  - 5P01CA65930-06/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.
DEP - 20030512
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (DNA Primers)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Base Sequence
MH  - Blotting, Western
MH  - Cell Differentiation
MH  - Cluster Analysis
MH  - DNA Primers
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Interleukin-6/physiology
MH  - Molecular Sequence Data
MH  - Oligonucleotide Array Sequence Analysis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thapsigargin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Protein p53/*physiology
PMC - PMC164513
EDAT- 2003/05/14 05:00
MHDA- 2003/07/17 05:00
PMCR- 2003/11/27
CRDT- 2003/05/14 05:00
PHST- 2003/05/14 05:00 [pubmed]
PHST- 2003/07/17 05:00 [medline]
PHST- 2003/05/14 05:00 [entrez]
PHST- 2003/11/27 00:00 [pmc-release]
AID - 1031695100 [pii]
AID - 1006718 [pii]
AID - 10.1073/pnas.1031695100 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2003 May 27;100(11):6718-23. doi: 
      10.1073/pnas.1031695100. Epub 2003 May 12.