PMID- 8137325
OWN - NLM
STAT- MEDLINE
DCOM- 19940425
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 54
IP  - 7 Suppl
DP  - 1994 Apr 1
TI  - Suppression of squamous cell carcinoma growth and differentiation by retinoids.
PG  - 1987s-1990s
AB  - The epithelium of the oral cavity is mostly nonkeratinizing. However, it 
      undergoes an abnormal squamous differentiation with keratinization during vitamin 
      A deficiency or oral carcinogenesis. Vitamin A analogues (retinoids) were found 
      to be effective in preventing oral premalignant lesions and second primary 
      cancers in the upper aerodigestive tract. Further development of retinoids for 
      prevention and therapy of squamous cell carcinoma (SCC) requires a better 
      understanding of their mechanism action on the growth and differentiation of SCC 
      cells. We used cultured head and neck SCC (HNSCC) cell lines as a model system. 
      Treatment of HNSCC cells with beta-all-trans-retinoic acid resulted in inhibition 
      of growth (proliferation and colony formation) and suppression of squamous 
      differentiation to varying degrees in the different cell lines. Because some of 
      the malignant HNSCC cells recapitulate the main characteristics of keratinocyte 
      squamous differentiation and responsiveness to retinoids, they can serve as a 
      model for investigating the mechanism underlying the effects of retinoids on cell 
      growth and differentiation. It is thought that nuclear retinoic acid receptors 
      (RARs) and retinoid X receptors (RXRs) mediate the above effects of retinoids by 
      acting as DNA-binding transcription-modulating factors. We found that HNSCC cell 
      lines express several nuclear RAR and that their level could be modulated by 
      retinoids in some cell lines. An inverse relationship was found between RAR-beta 
      expression and squamous differentiation. An analysis of RAR mRNA expression in 
      head and neck cancer specimens revealed a decrease in RAR-beta in premalignant 
      and malignant tissues relative to normal mucosa. The expression of this receptor 
      increased in vivo after treatment with 13-cis-retinoic acid. These results 
      implicate the loss of RAR-beta expression in the development of head and neck 
      cancer and suggest that RAR-beta could serve as an intermediate marker in 
      prevention trials.
FAU - Lotan, R
AU  - Lotan R
AD  - Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, 
      Houston 77030.
LA  - eng
GR  - P01-52051/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Anticarcinogenic Agents/*pharmacology
MH  - Carcinoma, Squamous Cell/drug therapy/*pathology/prevention & control
MH  - Cell Differentiation/*drug effects
MH  - Cell Division/*drug effects
MH  - Head and Neck Neoplasms/drug therapy/*pathology/prevention & control
MH  - Humans
MH  - Receptors, Cytoplasmic and Nuclear/physiology
MH  - Receptors, Retinoic Acid/physiology
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
RF  - 62
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1994 Apr 1;54(7 Suppl):1987s-1990s.