PMID- 17283128
OWN - NLM
STAT- MEDLINE
DCOM- 20070301
LR  - 20181109
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 3
DP  - 2007 Feb 1
TI  - The androgen receptor negatively regulates the expression of c-Met: implications 
      for a novel mechanism of prostate cancer progression.
PG  - 967-75
AB  - The precise molecular mechanisms by which prostate cancer cells progress from 
      androgen-sensitive to androgen-insensitive status still remain largely unclear. 
      The hepatocyte growth factor/scatter factor (HGF/SF) plays a critical role in the 
      regulation of cell growth, cell motility, morphogenesis, and angiogenesis. The 
      aberrant expression of HGF/SF and its receptor, c-Met, often correlates with poor 
      prognosis in a variety of human malignancies, including prostate cancer. Here, we 
      investigate a potential link between androgen signaling and c-Met expression in 
      prostate cancer cells. First, we showed that the androgen receptor (AR) represses 
      the expression of c-Met in a ligand-dependent manner. Using different c-Met 
      promoter/reporter constructs, we identified that Sp1 induces the transcription of 
      c-Met and that AR can repress the Sp1-induced transcription in prostate cancer 
      cells. Moreover, the data from electrophoretic mobility shift assay showed that 
      AR interferes with the interaction between Sp1 and the functional Sp1 binding 
      site within the c-Met promoter. Furthermore, we tested the effect of AR on c-Met 
      expression in an androgen-insensitive prostate cancer cell line, CWR22Rv1. 
      Finally, the repressive role of androgen signaling on c-Met expression was 
      confirmed in prostate cancer xenografts. The above data indicate a dual role of 
      AR in transcriptional regulation. Although the current androgen ablation therapy 
      can repress the expression of growth-promoting genes that are activated by the 
      AR, it may also attenuate the repressive role of AR on c-Met expression. 
      Therefore, the therapeutic strategies to inhibit the activation of the HGF/c-Met 
      pathway may be of benefit when combined with current androgen ablation treatment.
FAU - Verras, Meletios
AU  - Verras M
AD  - Departments of Urology and Genetics, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Lee, Jane
AU  - Lee J
FAU - Xue, Hui
AU  - Xue H
FAU - Li, Tzu-Huey
AU  - Li TH
FAU - Wang, Yuzhuo
AU  - Wang Y
FAU - Sun, Zijie
AU  - Sun Z
LA  - eng
GR  - R01 CA070297-07/CA/NCI NIH HHS/United States
GR  - R01 CA070297-11A2/CA/NCI NIH HHS/United States
GR  - CA 87767/CA/NCI NIH HHS/United States
GR  - R01 DK061002-03/DK/NIDDK NIH HHS/United States
GR  - R01 CA070297/CA/NCI NIH HHS/United States
GR  - R01 CA087767-03/CA/NCI NIH HHS/United States
GR  - R01 DK061002-04/DK/NIDDK NIH HHS/United States
GR  - R01 CA087767-02/CA/NCI NIH HHS/United States
GR  - R56 DK061002-06A1/DK/NIDDK NIH HHS/United States
GR  - R01 CA087767-05/CA/NCI NIH HHS/United States
GR  - R01 DK061002-05/DK/NIDDK NIH HHS/United States
GR  - DK 61002/DK/NIDDK NIH HHS/United States
GR  - R01 DK061002-01A1/DK/NIDDK NIH HHS/United States
GR  - R56 DK061002/DK/NIDDK NIH HHS/United States
GR  - R01 CA087767-01A2/CA/NCI NIH HHS/United States
GR  - R01 CA087767/CA/NCI NIH HHS/United States
GR  - R01 DK061002/DK/NIDDK NIH HHS/United States
GR  - R01 CA087767-04/CA/NCI NIH HHS/United States
GR  - R01 CA070297-08/CA/NCI NIH HHS/United States
GR  - R01 CA070297-12/CA/NCI NIH HHS/United States
GR  - R01 DK061002-02/DK/NIDDK NIH HHS/United States
GR  - R01 CA070297-09/CA/NCI NIH HHS/United States
GR  - CA 70297/CA/NCI NIH HHS/United States
GR  - R01 CA070297-10/CA/NCI NIH HHS/United States
GR  - R01 CA070297-06A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Sp1 Transcription Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Molecular Sequence Data
MH  - Promoter Regions, Genetic
MH  - Prostatic Neoplasms/genetics/*metabolism/*pathology
MH  - Proto-Oncogene Proteins c-met/*biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis/genetics
MH  - RNA, Small Interfering/genetics
MH  - Receptors, Androgen/deficiency/genetics/*metabolism
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/metabolism
MH  - Transfection
MH  - Transplantation, Heterologous
EDAT- 2007/02/07 09:00
MHDA- 2007/03/03 09:00
CRDT- 2007/02/07 09:00
PHST- 2007/02/07 09:00 [pubmed]
PHST- 2007/03/03 09:00 [medline]
PHST- 2007/02/07 09:00 [entrez]
AID - 67/3/967 [pii]
AID - 10.1158/0008-5472.CAN-06-3552 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Feb 1;67(3):967-75. doi: 10.1158/0008-5472.CAN-06-3552.