PMID- 10723137
OWN - NLM
STAT- MEDLINE
DCOM- 20000331
LR  - 20231213
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 19
IP  - 11
DP  - 2000 Mar 9
TI  - Modulation of retinoic acid receptor function alters the growth inhibitory 
      response of oral SCC cells to retinoids.
PG  - 1457-65
AB  - Retinoids have been shown to inhibit the growth of many human tumor cells 
      including breast, ovarian and squamous cell carcinoma (SCC). While the exact 
      mechanism of retinoid mediated growth suppression is not known, a role for the 
      retinoic acid receptors (RARs) and retinoid X receptors (RXRs) has been 
      established in both the breast and ovarian tumor cell models. We set out to 
      determine if modulation of RAR/RXR function would alter the retinoid sensitivity 
      of oral SCC cells. We found that the growth of SCC cells was significantly 
      inhibited by treatment with either all-trans-retinoic acid (trans-RA) or the 
      synthetic, conformationally restricted RARgamma selective retinoids MM11254 and 
      MM11389. In order to demonstrate a role for RAR/RXR function in this process, 
      stable oral SCC cell clones constitutively overexpressing the dominant negative 
      mutant RARbeta2 (R269Q) were prepared and shown to exhibit reduced RAR/RXR 
      transcriptional transactivation activity. We found that oral SCC cells exhibiting 
      reduced RAR/RXR function became resistant to growth inhibition by all-trans-RA, 
      MM11254 and MM11389. Likewise, treatment of oral SCC cells with the RARgamma 
      antagonist MM11253 was found to block the ability of MM11254 and MM11389 to 
      inhibit SCC cell growth. Thus, modulation of RAR function through the use of 
      RAR-gamma selective agonists, an RAR-gamma selective antagonist or a pan-RAR 
      dominant negative mutant significantly alters the growth inhibitory response of 
      oral SCC cells to retinoids.
FAU - Le, Q
AU  - Le Q
AD  - Fels Institute for Cancer Research and Molecular Biology, Temple University 
      School of Medicine, Philadelphia, Pennsylvania, PA 19140, USA.
FAU - Dawson, M I
AU  - Dawson MI
FAU - Soprano, D R
AU  - Soprano DR
FAU - Soprano, K J
AU  - Soprano KJ
LA  - eng
GR  - CA51993/CA/NCI NIH HHS/United States
GR  - CA64945/CA/NCI NIH HHS/United States
GR  - DK49045/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Growth Inhibitors)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoids)
RN  - 0 (retinoic acid receptor beta)
RN  - 0RH81L854J (Glutamine)
RN  - 5688UTC01R (Tretinoin)
RN  - 94ZLA3W45F (Arginine)
SB  - IM
MH  - Arginine/genetics
MH  - Carcinoma, Squamous Cell/genetics/*metabolism/pathology
MH  - Cell Division/drug effects/genetics
MH  - Gene Transfer Techniques
MH  - Glutamine/genetics
MH  - Growth Inhibitors/genetics/metabolism/*pharmacology
MH  - Humans
MH  - Mouth Neoplasms/genetics/*metabolism/pathology
MH  - Mutagenesis, Site-Directed
MH  - Receptors, Retinoic Acid/agonists/antagonists & 
      inhibitors/biosynthesis/genetics/metabolism/*physiology
MH  - Retinoids/chemical synthesis/*pharmacology
MH  - Tretinoin/pharmacology
MH  - Tumor Cells, Cultured
MH  - Retinoic Acid Receptor gamma
EDAT- 2000/03/21 00:00
MHDA- 2000/03/21 00:01
CRDT- 2000/03/21 00:00
PHST- 2000/03/21 00:00 [pubmed]
PHST- 2000/03/21 00:01 [medline]
PHST- 2000/03/21 00:00 [entrez]
AID - 10.1038/sj.onc.1203436 [doi]
PST - ppublish
SO  - Oncogene. 2000 Mar 9;19(11):1457-65. doi: 10.1038/sj.onc.1203436.