PMID- 14559809
OWN - NLM
STAT- MEDLINE
DCOM- 20031203
LR  - 20120605
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 63
IP  - 19
DP  - 2003 Oct 1
TI  - Conditional activation of fibroblast growth factor receptor (FGFR) 1, but not 
      FGFR2, in prostate cancer cells leads to increased osteopontin induction, 
      extracellular signal-regulated kinase activation, and in vivo proliferation.
PG  - 6237-43
AB  - Changes in the fibroblast growth factor receptor (FGFR) axis are often associated 
      with prostate cancer (CaP) progression. We have used chemically induced 
      dimerization (CID) to elucidate the individual contributions of FGFR1 and FGFR2 
      to tumor etiology. Novel CaP cell lines stably expressing CID/AP20187-inducible 
      FGFR1 (iFGFR1) and iFGFR2 were made using the tumorigenic transgenic 
      adenocarcinoma of the murine prostate (TRAMP)-derived clone, TRAMP-C2N (C2N), to 
      generate C2N.iFGFR1 or C2N.iFGFR2 cells. To test the effects of iFGFR activation 
      on tumor growth, mice bearing s.c. C2N.iFGFR1- or C2N.iFGFR2-derived tumors were 
      treated biweekly with CID. Activation of iFGFR1 led to rapid tumor growth as a 
      result of increased proliferation. In contrast, expression of iFGFR2 inhibited 
      tumor growth. Furthermore, we have ascertained that FGFR1 activation appears to 
      be most important during the early stages of tumor development, but once 
      established, tumors become rapidly CID independent. In these C2N-based lines, 
      quantitative signaling differences were seen between the two receptors, with 
      iFGFR1 leading to more robust extracellular signal-regulated kinase activation. 
      Additionally, activation of iFGFR1, but not iFGFR2, led to strong up-regulation 
      of osteopontin, a secreted glycoprotein involved in integrin activation and 
      associated with CaP progression and metastasis. These studies support the 
      hypothesis that observed changes in the FGFR axis in mammals during CaP 
      progression are causally important.
FAU - Freeman, Kevin W
AU  - Freeman KW
AD  - Department of Immunology, Baylor College of Medicine, One Baylor Plaza/M929, 
      Houston, TX 77030, USA.
FAU - Gangula, Rama D
AU  - Gangula RD
FAU - Welm, Bryan E
AU  - Welm BE
FAU - Ozen, Mustafa
AU  - Ozen M
FAU - Foster, Barbara A
AU  - Foster BA
FAU - Rosen, Jeffrey M
AU  - Rosen JM
FAU - Ittmann, Michael
AU  - Ittmann M
FAU - Greenberg, Norman M
AU  - Greenberg NM
FAU - Spencer, David M
AU  - Spencer DM
LA  - eng
GR  - R01 CA 87569/CA/NCI NIH HHS/United States
GR  - T32 AI 07495/AI/NIAID NIH HHS/United States
GR  - U01 CA 84296/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Receptors, Fibroblast Growth Factor)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, mouse)
RN  - 106441-73-0 (Osteopontin)
RN  - EC 2.7.10.1 (Fgfr1 protein, mouse)
RN  - EC 2.7.10.1 (Fgfr2 protein, mouse)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
RN  - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 2)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Adenocarcinoma/enzymology/genetics/*metabolism
MH  - Animals
MH  - Apoptosis/physiology
MH  - Cell Division/physiology
MH  - Cell Line, Tumor
MH  - Enzyme Activation
MH  - Gene Expression Regulation, Neoplastic
MH  - Male
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/*metabolism
MH  - Neoplasm Transplantation
MH  - Osteopontin
MH  - Phosphorylation
MH  - Prostatic Neoplasms/enzymology/genetics/*metabolism/pathology
MH  - Receptor Protein-Tyrosine Kinases/biosynthesis/genetics/*physiology
MH  - Receptor, Fibroblast Growth Factor, Type 1
MH  - Receptor, Fibroblast Growth Factor, Type 2
MH  - Receptors, Fibroblast Growth Factor/biosynthesis/genetics/*physiology
MH  - Sialoglycoproteins/*biosynthesis
MH  - Signal Transduction/physiology
MH  - Transfection
MH  - Up-Regulation
EDAT- 2003/10/16 05:00
MHDA- 2003/12/04 05:00
CRDT- 2003/10/16 05:00
PHST- 2003/10/16 05:00 [pubmed]
PHST- 2003/12/04 05:00 [medline]
PHST- 2003/10/16 05:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2003 Oct 1;63(19):6237-43.