PMID- 9010318
OWN - NLM
STAT- MEDLINE
DCOM- 19970220
LR  - 20190831
IS  - 0960-0760 (Print)
IS  - 0960-0760 (Linking)
VI  - 59
IP  - 3-4
DP  - 1996 Nov
TI  - Estrogen induction of TGF-alpha is mediated by an estrogen response element 
      composed of two imperfect palindromes.
PG  - 261-9
AB  - To investigate the molecular mechanisms underlying the two- to three-fold 
      induction of human transforming growth factor-alpha (hTGF-alpha) mRNA and two- to 
      five-fold induction of hTGF-alpha protein observed following estrogen treatment 
      of hormone-responsive human breast cancer cell lines, the hTGF-alpha promoter was 
      assayed for ERE-like sequences able to mediate estrogen induction of a 
      heterologous gene. Transient co-transfection of a chloramphenicol acetyl 
      transferase (CAT) construct consisting of either 1100 bp or 330 bp of hTGF-alpha 
      promoter sequence and an estrogen receptor expression vector into either COS-7 
      cells or hormonally responsive MCF-7 human breast cancer cells resulted in a two- 
      to five-fold induction of CAT activity by estrogen. Although no consensus 
      estrogen response element (ERE) exists in the hTGF-alpha promoter, a sequence 
      consisting of two imperfect ERE palindromes separated by 20 bp is located at -200 
      to -252. This sequence was inserted into a mouse mammary tumor virus (MMTV) based 
      CAT construct and assayed for its ability to confer estrogen regulation of CAT 
      expression to a heterologous promoter. Transient co-transfection of this 
      construct with an estrogen receptor expression vector into either COS-7 cells or 
      MCF-7 cells resulted in an average 30-fold estrogen induction of CAT activity. 
      Gel shift assays with human recombinant estrogen receptor (ER) and 32P-labelled 
      fragments revealed that the ER could specifically bind to this sequence. These 
      results indicate that this 53 bp sequence can function as an ERE, and is likely 
      to be responsible for the observed induction of TGF-alpha message and protein in 
      response to estrogen. These data also indicate that the level of estrogen 
      inducibility mediated by this element may be positively or negatively modulated 
      by interaction or competition with other transcription factors.
FAU - El-Ashry, D
AU  - El-Ashry D
AD  - Lombardi Cancer Center, Department of Biochemistry, Georgetown University Medical 
      Center, N.W., Washington, DC 20007, USA.
FAU - Chrysogelos, S A
AU  - Chrysogelos SA
FAU - Lippman, M E
AU  - Lippman ME
FAU - Kern, F G
AU  - Kern FG
LA  - eng
GR  - CA50376/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 4TI98Z838E (Estradiol)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Breast Neoplasms/*metabolism
MH  - COS Cells
MH  - Carcinoma/metabolism
MH  - Chloramphenicol O-Acetyltransferase/genetics
MH  - Consensus Sequence
MH  - DNA/metabolism
MH  - Estradiol/metabolism/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects/*genetics
MH  - Humans
MH  - Mammary Tumor Virus, Mouse
MH  - Mice
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic/*genetics
MH  - RNA, Messenger/biosynthesis
MH  - Receptors, Estrogen/physiology
MH  - Recombinant Fusion Proteins
MH  - Repetitive Sequences, Nucleic Acid/genetics
MH  - Transfection
MH  - Transforming Growth Factor alpha/*genetics
MH  - Tumor Cells, Cultured
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - S0960-0760(96)00118-5 [pii]
AID - 10.1016/s0960-0760(96)00118-5 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 1996 Nov;59(3-4):261-9. doi: 
      10.1016/s0960-0760(96)00118-5.