PMID- 19109434
OWN - NLM
STAT- MEDLINE
DCOM- 20090213
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 1
DP  - 2009 Jan 6
TI  - Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without 
      affecting primary tumor formation.
PG  - 151-6
LID - 10.1073/pnas.0808703105 [doi]
AB  - Steroid receptor coactivator-1 (SRC-1) is a coactivator for nuclear hormone 
      receptors such as estrogen and progesterone receptors and certain other 
      transcription factors such as Ets-2 and PEA3. SRC-1 expression in breast cancer 
      is associated with HER2 and c-Myc expression and with reduced disease-free 
      survival. In this study, SRC-1(-/-) mice were backcrossed with FVB mice and then 
      cross-bred with MMTV-polyoma middle T antigen (PyMT) mice to investigate the role 
      of SRC-1 in breast cancer. Although mammary tumor initiation and growth were 
      similar in SRC-1(-/-)/PyMT and wild-type (WT)/PyMT mice, genetic ablation of 
      SRC-1 antagonized PyMT-induced restriction of mammary ductal differentiation and 
      elongation. SRC-1(-/-)/PyMT mammary tumors were also more differentiated than 
      WT/PyMT mammary tumors. The intravasation of mammary tumor cells and the 
      frequency and extent of lung metastasis were drastically reduced in 
      SRC-1(-/-)/PyMT mice compared with WT/PyMT mice. Metastatic analysis of 
      transplanted WT/PyMT and SRC-1(-/-)/PyMT tumors in SRC-1(-/-) and WT recipient 
      mice revealed that SRC-1 played an intrinsic role in tumor cell metastasis. 
      Furthermore, SRC-1 was up-regulated during mammary tumor progression. Disruption 
      of SRC-1 inhibited Ets-2-mediated HER2 expression and PyMT-stimulated Akt 
      activation in the mammary tumors. Disruption of SRC-1 also suppressed 
      colony-stimulating factor-1 (CSF-1) expression and reduced macrophage recruitment 
      to the tumor site. These results suggest that SRC-1 specifically promotes 
      metastasis without affecting primary tumor growth. SRC-1 may promote metastasis 
      through mediating Ets-2-mediated HER2 expression and activating CSF-1 expression 
      for macrophage recruitment. Therefore, functional interventions for coactivators 
      like SRC-1 may provide unique approaches to control breast cancer progression and 
      metastasis.
FAU - Wang, Shu
AU  - Wang S
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, One 
      Baylor Plaza, Houston, TX 77030, USA.
FAU - Yuan, Yuhui
AU  - Yuan Y
FAU - Liao, Lan
AU  - Liao L
FAU - Kuang, Shao-Qing
AU  - Kuang SQ
FAU - Tien, Jean Ching-Yi
AU  - Tien JC
FAU - O'Malley, Bert W
AU  - O'Malley BW
FAU - Xu, Jianming
AU  - Xu J
LA  - eng
GR  - P01 DK059820-099003/DK/NIDDK NIH HHS/United States
GR  - R01 CA119689-05/CA/NCI NIH HHS/United States
GR  - DK58242/DK/NIDDK NIH HHS/United States
GR  - R01 DK058242-05/DK/NIDDK NIH HHS/United States
GR  - P01 DK059820/DK/NIDDK NIH HHS/United States
GR  - CA112403/CA/NCI NIH HHS/United States
GR  - CA119689/CA/NCI NIH HHS/United States
GR  - R01 CA112403/CA/NCI NIH HHS/United States
GR  - R01 CA112403-03/CA/NCI NIH HHS/United States
GR  - DK59820/DK/NIDDK NIH HHS/United States
GR  - R01 DK058242/DK/NIDDK NIH HHS/United States
GR  - R01 CA119689/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081224
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 (Proto-Oncogene Protein c-ets-2)
RN  - 0 (Transcription Factors)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.10.1 (Erbb2 protein, mouse)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Breast Neoplasms/etiology/genetics/*pathology
MH  - Cell Differentiation
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Histone Acetyltransferases/*genetics
MH  - Macrophage Colony-Stimulating Factor/genetics
MH  - Mice
MH  - Mice, Knockout
MH  - Neoplasm Metastasis/genetics/*pathology
MH  - Neoplasm Transplantation
MH  - Nuclear Receptor Coactivator 1
MH  - Proto-Oncogene Protein c-ets-2/genetics
MH  - Receptor, ErbB-2/genetics
MH  - Transcription Factors/*genetics
PMC - PMC2629242
COIS- The authors declare no conflict of interest.
EDAT- 2008/12/26 09:00
MHDA- 2009/02/14 09:00
PMCR- 2009/07/06
CRDT- 2008/12/26 09:00
PHST- 2008/12/26 09:00 [entrez]
PHST- 2008/12/26 09:00 [pubmed]
PHST- 2009/02/14 09:00 [medline]
PHST- 2009/07/06 00:00 [pmc-release]
AID - 0808703105 [pii]
AID - 5245 [pii]
AID - 10.1073/pnas.0808703105 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):151-6. doi: 10.1073/pnas.0808703105. 
      Epub 2008 Dec 24.