PMID- 15318936
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20220224
IS  - 1465-542X (Electronic)
IS  - 1465-5411 (Print)
IS  - 1465-5411 (Linking)
VI  - 6
IP  - 5
DP  - 2004
TI  - A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is 
      potentially a therapeutic target in breast cancer cell lines, and that it 
      potentiates antiproliferative and apoptotic responses to peroxisome 
      proliferator-activated receptor ligands.
PG  - R546-55
AB  - INTRODUCTION: Certain lipids have been shown to be ligands for a subgroup of the 
      nuclear hormone receptor superfamily known as the peroxisome 
      proliferator-activated receptors (PPARs). Ligands for these transcription factors 
      have been used in experimental cancer therapies. PPARs heterodimerize and bind 
      DNA with retinoid X receptors (RXRs), which have homology to other members of the 
      nuclear receptor superfamily. Retinoids have been found to be effective in 
      treating many types of cancer. However, many breast cancers become resistant to 
      the chemotherapeutic effects of these drugs. Recently, RXR-selective ligands were 
      discovered that inhibited proliferation of all-trans retinoic acid resistant 
      breast cancer cells in vitro and caused regression of the disease in animal 
      models. There are few published studies on the efficacy of combined therapy using 
      PPAR and RXR ligands for breast cancer prevention or treatment. METHODS: We 
      determined the effects of selective PPAR and RXR ligands on established human 
      breast cancer cell lines in vitro. RESULTS: PPAR-alpha and PPAR-gamma ligands 
      induced apoptotic and antiproliferative responses in human breast cancer cell 
      lines, respectively, which were associated with specific changes in gene 
      expression. These responses were potentiated by the RXR-selective ligand 
      AGN194204. Interestingly, RXR-alpha-overexpressing retinoic acid resistant breast 
      cancer cell lines were more sensitive to the effects of the RXR-selective 
      compound. CONCLUSION: RXR-selective retinoids can potentiate the 
      antiproliferative and apoptotic responses of breast cancer cell lines to PPAR 
      ligands.
FAU - Crowe, David L
AU  - Crowe DL
AD  - Center for Craniofacial Molecular Biology, University of Southern California, Los 
      Angeles, California, USA. dcrowe@usc.edu
FAU - Chandraratna, Roshantha A S
AU  - Chandraratna RA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040723
PL  - England
TA  - Breast Cancer Res
JT  - Breast cancer research : BCR
JID - 100927353
RN  - 0 (AGN 194204)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Ligands)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
RN  - 78YC2MAX4O (gamma-Linolenic Acid)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/*genetics/metabolism/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Division/drug effects
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins
MH  - Drug Resistance, Neoplasm/genetics
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Gene Expression
MH  - Humans
MH  - *Ligands
MH  - Nuclear Proteins
MH  - *Receptors, Cytoplasmic and Nuclear/genetics/metabolism
MH  - *Receptors, Retinoic Acid/genetics/metabolism
MH  - Retinoid X Receptors
MH  - Tetrahydronaphthalenes/pharmacology
MH  - *Transcription Factors/genetics/metabolism
MH  - Tretinoin/pharmacology
MH  - gamma-Linolenic Acid/pharmacology
PMC - PMC549174
EDAT- 2004/08/21 05:00
MHDA- 2004/10/06 09:00
PMCR- 2004/07/23
CRDT- 2004/08/21 05:00
PHST- 2003/11/02 00:00 [received]
PHST- 2004/06/15 00:00 [revised]
PHST- 2004/06/24 00:00 [accepted]
PHST- 2004/08/21 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/08/21 05:00 [entrez]
PHST- 2004/07/23 00:00 [pmc-release]
AID - bcr913 [pii]
AID - 10.1186/bcr913 [doi]
PST - ppublish
SO  - Breast Cancer Res. 2004;6(5):R546-55. doi: 10.1186/bcr913. Epub 2004 Jul 23.