PMID- 15917309
OWN - NLM
STAT- MEDLINE
DCOM- 20051108
LR  - 20201209
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 26
IP  - 10
DP  - 2005 Oct
TI  - The p160 family coactivators regulate breast cancer cell proliferation and 
      invasion through autocrine/paracrine activity of SDF-1alpha/CXCL12.
PG  - 1706-15
AB  - Estrogen receptors (ERs) regulate the transcription of genes involved in breast 
      cancer cell proliferation, invasion and metastasis. In addition to ligand 
      concentration, phosphorylation and coactivator/corepressor levels control 
      ER-dependent transcription. In this study, we used MCF-7 breast cancer sublines 
      with variable levels of the steroid receptor coactivator 1 (SRC-1) to investigate 
      the importance of coactivator levels in basal and estrogen-inducible expression 
      of SDF-1alpha/CXCL12, cathepsin D and cMyc. Basal expression of SDF-1alpha and 
      cMyc but not of cathepsin D was substantially lower in a MCF-7 subline lacking 
      SRC-1 ((MCF-7/p2) compared with MCF-7 sublines expressing SRC-1 (MCF-7/p1 and 
      LCC2). Although estrogen efficiently induced SDF-1alpha in MCF-7/p1 cells, very 
      little induction of this gene was observed in MCF-7/p2 cells. The absence of 
      SRC-1 had no effect on estrogen-inducible expression cMyc and cathepsin D 
      suggesting that coactivator levels determine the expression of only a subset of 
      estrogen-regulated genes. Introduction of SRC-1, SRC-2/TIF-2 or SRC-3/AIB1 
      increased basal expression of SDF-1alpha in MCF-7/p2 cells. Consistent with the 
      role of SDF-1alpha in mediating estrogen-induced proliferation, estrogen failed 
      to increase proliferation of MCF-7/p2 cells. In matrigel invasion assays, 
      conditioned media from MCF-7/p1 but not MCF-7/p2 cells increased invasion of 
      cancer cells expressing metastasis-associated genes and CXCR4, the receptor for 
      SDF-1alpha. These results suggest that coactivators control SDF-1alpha 
      expression, which mediates estrogen-induced proliferation and invasion through 
      autocrine and paracrine mechanisms, respectively. These results also provide a 
      molecular explanation for recent observations linking co-overexpression of 
      coactivators and her2/neu with poor prognosis: coactivators increase SDF-1alpha 
      expression whereas her2/neu stabilize CXCR4 protein.
FAU - Kishimoto, Hiromitsu
AU  - Kishimoto H
AD  - Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 
      46202, USA.
FAU - Wang, Zhuo
AU  - Wang Z
FAU - Bhat-Nakshatri, Poornima
AU  - Bhat-Nakshatri P
FAU - Chang, David
AU  - Chang D
FAU - Clarke, Robert
AU  - Clarke R
FAU - Nakshatri, Harikrishna
AU  - Nakshatri H
LA  - eng
GR  - R01CA89153/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050525
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chemokines, CXC)
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogens)
RN  - 0 (MYBBP1A protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nucleocytoplasmic Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Transcription Factors)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Breast Neoplasms/*pathology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - Chemokine CXCL12
MH  - Chemokines, CXC/genetics/*metabolism
MH  - Chloramphenicol O-Acetyltransferase/genetics/metabolism
MH  - DNA Primers
MH  - DNA-Binding Proteins
MH  - Estrogens/pharmacology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Reporter
MH  - Humans
MH  - Neoplasm Invasiveness
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Nucleocytoplasmic Transport Proteins
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering
MH  - RNA-Binding Proteins
MH  - Receptors, CXCR4/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tamoxifen/pharmacology
MH  - Transcription Factors
MH  - Transfection
EDAT- 2005/05/27 09:00
MHDA- 2005/11/09 09:00
CRDT- 2005/05/27 09:00
PHST- 2005/05/27 09:00 [pubmed]
PHST- 2005/11/09 09:00 [medline]
PHST- 2005/05/27 09:00 [entrez]
AID - bgi137 [pii]
AID - 10.1093/carcin/bgi137 [doi]
PST - ppublish
SO  - Carcinogenesis. 2005 Oct;26(10):1706-15. doi: 10.1093/carcin/bgi137. Epub 2005 
      May 25.