PMID- 7923214
OWN - NLM
STAT- MEDLINE
DCOM- 19941123
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 54
IP  - 21
DP  - 1994 Nov 1
TI  - A specific defect in the retinoic acid response associated with human lung cancer 
      cell lines.
PG  - 5663-9
AB  - The effects of retinoic acid (RA) are mainly mediated by its nuclear receptors, 
      the RA receptors (RARs) and retinoid X receptors (RXRs) that regulate target gene 
      expression by binding to specific RA-response elements (RAREs). RAR beta is the 
      best characterized RA-responsive gene. Due to the presence of a RARE (beta RARE) 
      in its promoter, the expression of the RAR beta 2 is markedly increased in 
      response to RA in most epithelial tissues, including lung. Recently, it was 
      observed that the RAR beta gene is not expressed in a number of human lung cancer 
      cell lines, suggesting a possible correlation between abnormal expression of the 
      RAR beta gene and lung cancer development. In this study, we investigate the RA 
      response in human lung cancer cell lines. Here we report that the expression of 
      the RAR beta gene cannot be regulated by RA in the majority of human lung cancer 
      cell lines examined, while the general response to RA is intact. The 
      nonresponsiveness of the RAR beta gene results from different defects in the 
      response mechanism. Interestingly, we find in some cell lines a differential 
      responsiveness of the beta RARE such that the element is inactive in its natural 
      promoter context but active when linked to the heterologous tk promoter. 
      Importantly, we also observe that the presence of retinoid receptors is not 
      sufficient for the induction of the RAR beta gene. This suggests that specific 
      factors determine the RA responsiveness in the context of its natural promoter. 
      Our observation that the RA nonresponsiveness of the RAR beta promoter is a 
      common feature of human lung cancer cell lines suggests that balanced RAR beta 
      expression is an essential feature for the maintenance of a normal state of lung 
      tissue.
FAU - Zhang, X K
AU  - Zhang XK
AD  - La Jolla Cancer Research Foundation, California 92037.
FAU - Liu, Y
AU  - Liu Y
FAU - Lee, M O
AU  - Lee MO
FAU - Pfahl, M
AU  - Pfahl M
LA  - eng
GR  - CA50676/CA/NCI NIH HHS/United States
GR  - CA60988/CA/NCI 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 (Receptors, Retinoic Acid)
RN  - 5688UTC01R (Tretinoin)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
GS  - RAR&Bgr;
MH  - Blotting, Northern
MH  - Chloramphenicol O-Acetyltransferase/genetics/metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects/*genetics
MH  - Genes, Reporter/physiology
MH  - Humans
MH  - Lung Neoplasms/chemistry/*genetics
MH  - Promoter Regions, Genetic/physiology
MH  - Receptors, Retinoic Acid/analysis/classification/drug effects/*genetics
MH  - Tretinoin/*pharmacology
MH  - Tumor Cells, Cultured
EDAT- 1994/11/01 00:00
MHDA- 1994/11/01 00:01
CRDT- 1994/11/01 00:00
PHST- 1994/11/01 00:00 [pubmed]
PHST- 1994/11/01 00:01 [medline]
PHST- 1994/11/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1994 Nov 1;54(21):5663-9.