PMID- 20103632
OWN - NLM
STAT- MEDLINE
DCOM- 20100309
LR  - 20211028
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 3
DP  - 2010 Feb 1
TI  - BRCA1 represses amphiregulin gene expression.
PG  - 996-1005
LID - 10.1158/0008-5472.CAN-09-2842 [doi]
AB  - BRCA1, the breast cancer- and ovarian cancer-specific tumor suppressor, can be a 
      transcriptional repressor or a transcriptional activator, depending on the 
      promoter context. To identify the genes activated or repressed by BRCA1, we have 
      analyzed microarray results from cells depleted of BRCA1 and revealed a number of 
      genes regulated by BRCA1 on the level of transcription. Among the genes repressed 
      by BRCA1, we have identified amphiregulin (AREG) and early growth response-1 
      (EGR1). Results indicate that BRCA1 regulates AREG transcription directly through 
      binding to the AREG promoter, however, we could not detect BRCA1 on the EGR1 
      promoter, suggesting that EGR1 is indirectly regulated by BRCA1. In an attempt to 
      identify the mechanism of the AREG transcriptional repression by BRCA1, we have 
      mapped two independent BRCA1 response elements on the AREG located at positions 
      -202/-182 and +19/+122. BRCA1 depletion leads to induction of the AREG protein. 
      Taken together, our data build the connection between BRCA1 loss of function and 
      AREG upregulation-a change in gene expression often observed in breast cancer.
FAU - Lamber, Ekaterina P
AU  - Lamber EP
AD  - Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
FAU - Horwitz, Andrew A
AU  - Horwitz AA
FAU - Parvin, Jeffrey D
AU  - Parvin JD
LA  - eng
GR  - A7640/CRUK_/Cancer Research UK/United Kingdom
GR  - R01 CA090281/CA/NCI NIH HHS/United States
GR  - CA90281/CA/NCI NIH HHS/United States
GR  - C423/A7640/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100126
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (BRCA1 Protein)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Amphiregulin
MH  - BRCA1 Protein/genetics/*metabolism
MH  - Binding Sites/genetics
MH  - Blotting, Western
MH  - Breast Neoplasms/genetics/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Chromatin Immunoprecipitation
MH  - EGF Family of Proteins
MH  - Early Growth Response Protein 1/genetics/metabolism
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glycoproteins/*genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding
MH  - RNA Interference
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC2816672
MID - UKMS28246
OID - NLM: UKMS28246
EDAT- 2010/01/28 06:00
MHDA- 2010/03/10 06:00
PMCR- 2010/08/01
CRDT- 2010/01/28 06:00
PHST- 2010/01/28 06:00 [entrez]
PHST- 2010/01/28 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
PHST- 2010/08/01 00:00 [pmc-release]
AID - 0008-5472.CAN-09-2842 [pii]
AID - 10.1158/0008-5472.CAN-09-2842 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Feb 1;70(3):996-1005. doi: 10.1158/0008-5472.CAN-09-2842. Epub 
      2010 Jan 26.