PMID- 11340568
OWN - NLM
STAT- MEDLINE
DCOM- 20010524
LR  - 20231213
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 92
IP  - 5
DP  - 2001 Jun 1
TI  - Expression of retinoic acid receptor gamma correlates with retinoic acid 
      sensitivity and metabolism in head and neck squamous cell carcinoma cell lines.
PG  - 661-5
AB  - Retinoids, analogues of vitamin A, can reverse premalignant lesions and prevent 
      second primary tumors in patients with head and neck squamous cell carcinoma 
      (HNSCC). The effects of retinoids are mediated by retinoic acid receptors (RARs) 
      and retinoid X receptors (RXRs), which act as ligand-activated transcription 
      factors. The regulation of cell growth, differentiation and retinoid metabolism 
      in normal, premalignant and malignant cells by retinoids is thought to be a 
      result of their effects on gene expression. We investigated mRNA expression of 
      RARs (alpha, beta, and gamma) and RXR-beta by means of RNase protection and 
      related this to retinoic acid (RA)-induced growth inhibition and RA turnover in 
      four HNSCC cell lines (UM-SCC-14C, UM-SCC-22A, UM-SCC-35 and VU-SCC-OE). An 
      RA-resistant subline of UM-SCC-35 was generated by exposure to increasing 
      concentrations of RA for 8 months (designated UM-SCC-35R). RA turnover was 
      determined on the basis of decreasing RA levels in the cells and culture medium 
      after exposure to 1 microM RA. We found that RAR-gamma mRNA expression was 
      strongly correlated with RA-induced growth inhibition (p = 0.016, R = 0.92) and 
      RA turnover (p = 0.041, R = 0.86). RAR-beta transcript levels were reduced in 
      three of five cell lines compared with normal mucosa, and these did not correlate 
      with RA-induced growth inhibition and RA turnover. Expression of RAR-alpha and 
      RXR-beta was not substantially altered in any of the cell lines. These findings 
      suggest that in HNSCC cell lines RAR-gamma is the most important retinoid 
      receptor for regulation of RA turnover rate and RA-induced growth inhibition.
CI  - Copyright 2001 Wiley-Liss, Inc.
FAU - Klaassen, I
AU  - Klaassen I
AD  - Section of Tumor Biology, Department of Otolaryngology/Head and Neck Surgery, 
      University Hospital Vrije Universiteit, 1007 MB Amsterdam, the Netherlands.
FAU - Brakenhoff, R H
AU  - Brakenhoff RH
FAU - Smeets, S J
AU  - Smeets SJ
FAU - Snow, G B
AU  - Snow GB
FAU - Braakhuis, B J
AU  - Braakhuis BJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (retinoic acid receptor beta)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Carcinoma, Squamous Cell/*drug therapy/metabolism
MH  - Head and Neck Neoplasms/*drug therapy/metabolism
MH  - Humans
MH  - RNA, Messenger/analysis
MH  - Receptors, Retinoic Acid/*genetics/physiology
MH  - Tretinoin/metabolism/*pharmacology
MH  - Tumor Cells, Cultured
MH  - Retinoic Acid Receptor gamma
EDAT- 2001/05/08 10:00
MHDA- 2001/05/26 10:01
CRDT- 2001/05/08 10:00
PHST- 2001/05/08 10:00 [pubmed]
PHST- 2001/05/26 10:01 [medline]
PHST- 2001/05/08 10:00 [entrez]
AID - 10.1002/1097-0215(20010601)92:5<661::AID-IJC1251>3.0.CO;2-O [pii]
AID - 10.1002/1097-0215(20010601)92:5<661::aid-ijc1251>3.0.co;2-o [doi]
PST - ppublish
SO  - Int J Cancer. 2001 Jun 1;92(5):661-5. doi: 
      10.1002/1097-0215(20010601)92:5<661::aid-ijc1251>3.0.co;2-o.