PMID- 15618235
OWN - NLM
STAT- MEDLINE
DCOM- 20050413
LR  - 20061115
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 26
IP  - 3
DP  - 2005 Mar
TI  - Comprehensive expression analysis of retinoic acid receptors and retinoid X 
      receptors in non-small cell lung cancer: implications for tumor development and 
      prognosis.
PG  - 525-30
AB  - Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are important in 
      regulating the development, growth and differentiation of cells and have 
      inhibitory effects on non-small cell lung cancer (NSCLC) cell growth. A 
      comprehensive analysis of all RAR and RXR subtypes mRNA expression in a large 
      series of patients with NSCLC and their role in the development and progression 
      of this disease is lacking. Using a quantitative real-time RT-PCR method, we 
      analyzed the mRNA expression of all retinoid receptor subtypes in tumor and 
      matching normal-appearing tissues of 88 patients with NSCLC. Gene expression in 
      tumor tissues was detected with the following frequencies: RARalpha 100%, RARbeta 
      94%, RARgamma 94%, RXRalpha 100%, RXRbeta 100% and RXRgamma 92%. Levels of mRNA 
      expression in tumor tissues compared with matching normal-appearing tissue were 
      equal or reduced with the following frequencies: RARalpha 76.1%, RARbeta 59.1%, 
      RARgamma 39.8%, RXRalpha 67.1%, RXRbeta 54.5% and RXRgamma 88.6%, and were 
      significantly associated with any one other subtype. The probability of survival 
      was significantly different among patients with low gene expression in no or any 
      two subtypes, any three or four subtypes or any five or six subtypes (P = 0.004, 
      log rank test). Multivariate analysis confirmed low gene expression status as a 
      significant independent unfavorable prognostic factor (P = 0.015). Our results 
      show that decreased expression of all RAR and RXR receptor subtypes is a frequent 
      event in NSCLC. Widely co-regulated down-regulation of expression of all retinoid 
      subclasses suggests a fundamental dysregulation of the retinoid pathway in this 
      cancer. Quantitation of RAR and RXR mRNA expression levels in tumor tissue is a 
      candidate prognostic marker and surrogate biomarker for chemopreventive trials in 
      NSCLC.
FAU - Brabender, Jan
AU  - Brabender J
AD  - Department of Visceral and Vascular Surgery, University of Cologne, 
      Joseph-Stelzmann Strasse 9, 50931 Cologne, Germany. jan.brabender@t-online.de
FAU - Metzger, Ralf
AU  - Metzger R
FAU - Salonga, Dennis
AU  - Salonga D
FAU - Danenberg, Kathleen D
AU  - Danenberg KD
FAU - Danenberg, Peter V
AU  - Danenberg PV
FAU - Holscher, Arnulf H
AU  - Holscher AH
FAU - Schneider, Paul M
AU  - Schneider PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041223
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (DNA Primers)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Base Sequence
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism/pathology
MH  - DNA Primers
MH  - Humans
MH  - Lung Neoplasms/*metabolism/pathology
MH  - Prognosis
MH  - Receptors, Retinoic Acid/*metabolism
MH  - Retinoid X Receptors/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2004/12/25 09:00
MHDA- 2005/04/14 09:00
CRDT- 2004/12/25 09:00
PHST- 2004/12/25 09:00 [pubmed]
PHST- 2005/04/14 09:00 [medline]
PHST- 2004/12/25 09:00 [entrez]
AID - bgi006 [pii]
AID - 10.1093/carcin/bgi006 [doi]
PST - ppublish
SO  - Carcinogenesis. 2005 Mar;26(3):525-30. doi: 10.1093/carcin/bgi006. Epub 2004 Dec 
      23.