PMID- 10542244
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Mechanisms of transcriptional activation of bcl-2 gene expression by
      17beta-estradiol in breast cancer cells.
PG  - 32099-107
AB  - bcl-2 gene expression is induced by 17beta-estradiol (E2) in T47D and MCF-7 human
      breast cancer cells, and the mechanism of E2 responsiveness was further
      investigated by analysis of the bcl-2 gene promoter. The -1602 to -1534 distal
      region (bcl-2j) of the promoter was E2-responsive; however, in gel mobility shift
      assays, the estrogen receptor alpha (ER(alpha)) did not bind [(32)P]bcl-2j,
      whereas Sp1 protein formed a retarded band complex. Further analysis demonstrated
      that the upstream region (-1603 to -1579) of the bcl-2 gene promoter contained
      two GC/GA-rich sites at -1601 (5'-GGGCTGG-3') and -1588 (3'-GGAGGG-5') that bound
      Sp1 protein. Subsequent studies confirmed that transactivation by E2 was
      dependent on ER(alpha)/Sp1 interactions with both GC-rich sites, and this was
      confirmed by in vitro footprinting. In contrast, a 21-base pair E2-responsive
      downstream region (-1578 to -1534) did not bind Sp1 or ER(alpha) protein;
      however, analysis of a complex binding pattern with nuclear extracts showed that 
      ATF-1 and CREB-1 bound to this motif. These data coupled with results of
      transient transfection studies demonstrated that transcriptional activation by E2
      of the -1578 to -1534 region of the bcl-2 gene promoter was dependent on
      induction of cAMP and subsequent activation through a cAMP response element.
      Thus, hormone regulation of bcl-2 gene expression in breast cancer cells involves
      multiple enhancer elements and E2-mediated transactivation does not require
      direct binding of the estrogen receptor with promoter DNA.
FAU - Dong, L
AU  - Dong L
AD  - Department of Veterinary Physiology, Texas A&M University, College Station, Texas
      77843, USA.
FAU - Wang, W
AU  - Wang W
FAU - Wang, F
AU  - Wang F
FAU - Stoner, M
AU  - Stoner M
FAU - Reed, J C
AU  - Reed JC
FAU - Harigai, M
AU  - Harigai M
FAU - Samudio, I
AU  - Samudio I
FAU - Kladde, M P
AU  - Kladde MP
FAU - Vyhlidal, C
AU  - Vyhlidal C
FAU - Safe, S
AU  - Safe S
LA  - eng
GR  - CA76636/CA/NCI NIH HHS/United States
GR  - ES09106/ES/NIEHS 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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Activating Transcription Factor 1)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Activating Transcription Factor 1
MH  - Base Sequence
MH  - Breast Neoplasms/*genetics
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - *DNA-Binding Proteins
MH  - Estradiol/*physiology
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - *Genes, bcl-2/*genetics
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oligonucleotides/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - Transcription Factors/metabolism
MH  - *Transcriptional Activation
MH  - Tumor Cells, Cultured
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32099 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32099-107. doi: 10.1074/jbc.274.45.32099.