PMID- 10537322
OWN - NLM
STAT- MEDLINE
DCOM- 19991110
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 59
IP  - 20
DP  - 1999 Oct 15
TI  - Distinctive expression and functions of the type 4 endothelial differentiation
      gene-encoded G protein-coupled receptor for lysophosphatidic acid in ovarian
      cancer.
PG  - 5370-5
AB  - Endothelial differentiation gene (edg)-encoded G protein-coupled receptors (Edg
      Rs)-1, -3, and -5 bind sphingosine 1-phosphate (S1P), and Edg-2 and -4 bind
      lysophosphatidic acid (LPA). Edg Rs transduce signals from LPA and S1P that
      stimulate ras- and rho-dependent cellular proliferation, enhance cellular
      survival, and suppress apoptosis. That high levels of LPA in plasma and ascitic
      fluid of patients with ovarian cancer correlate with widespread invasion
      suggested the importance of investigating expression and functions of Edg Rs in
      ovarian cancer cells (OCCs) as compared with nonmalignant ovarian surface
      epithelial cells (OSEs). Analyses of Edg Rs by semiquantitative reverse
      transcription-PCR, a radioactively quantified variant of PCR, and Western blots
      developed with monoclonal antibodies showed prominent expression of Edg-4 R in
      primary cultures and established lines of OCCs but none in OSEs. In contrast,
      levels of Edg-2, -3, and -5 were higher in OSEs than OCCs. LPA stimulated
      proliferation and signaled a serum response element-luciferase reporter of
      immediate-early gene activation in OCCs but not OSEs, whereas S1P evoked similar 
      responses in both OSEs and OCCs. Pharmacological inhibitors of Edg R signaling
      suppressed OCC responses to LPA. A combination of monoclonal anti-Edg-4 R
      antibody and phorbol myristate acetate, which were inactive separately, evoked
      proliferative and serum response element-luciferase responses of OCCs but not
      OSEs. Thus the Edg-4 R may represent a distinctive marker of OCC that transduces 
      growth-promoting signals from the high local concentrations of LPA characteristic
      of aggressive ovarian cancer.
FAU - Goetzl, E J
AU  - Goetzl EJ
AD  - Department of Medicine and Microbiology-Immunology, University of California, San
      Francisco 94143, USA. egoetzl@itsa.ucsf.edu
FAU - Dolezalova, H
AU  - Dolezalova H
FAU - Kong, Y
AU  - Kong Y
FAU - Hu, Y L
AU  - Hu YL
FAU - Jaffe, R B
AU  - Jaffe RB
FAU - Kalli, K R
AU  - Kalli KR
FAU - Conover, C A
AU  - Conover CA
LA  - eng
GR  - HL31809/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Lysophospholipids)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Lysophosphatidic Acid)
RN  - 0 (Transcription Factors)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - NGZ37HRE42 (Sphingosine)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Female
MH  - Humans
MH  - Insulin-Like Growth Factor II/biosynthesis
MH  - Lysophospholipids/pharmacology
MH  - Nuclear Proteins/analysis
MH  - Ovarian Neoplasms/*chemistry/pathology
MH  - RNA, Messenger/analysis
MH  - Receptors, Cell Surface/*analysis/genetics/physiology
MH  - *Receptors, G-Protein-Coupled
MH  - Receptors, Lysophosphatidic Acid
MH  - Response Elements
MH  - Signal Transduction
MH  - Sphingosine/analogs & derivatives/pharmacology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/analysis
EDAT- 1999/10/28 00:00
MHDA- 1999/10/28 00:01
CRDT- 1999/10/28 00:00
PHST- 1999/10/28 00:00 [pubmed]
PHST- 1999/10/28 00:01 [medline]
PHST- 1999/10/28 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1999 Oct 15;59(20):5370-5.