Implication of retinoic acid receptor γ in squamous differentiation and response to retinoic acid in head and neck SqCC/Y1 squamous carcinoma cells

Nobuhiko Oridate, Noriko Esumi, Dafna Lotan, Waun Ki Hong, Cecil Rochette-Egly, Pierre Chambon, Reuben Lotan

Research output: Contribution to journalArticle

Abstract

Nuclear retinoic acid receptors are considered to be the mediators of most of the effects of retinoic acid (RA) on gene expression. To explore the role of RA receptor γ (RARγ) in the growth and differentiation of SqCC/Y1 head and neck squamous carcinoma cells, they were transfected with RARγ sense and antisense expression vectors and stable clones in which RARγ expression was either increased or blocked were isolated. The growth inhibitory effect of RA in monolayer culture was enhanced in the sense transfectants and decreased in the antisense ones. The ability to form colonies in semisolid medium was abolished by RA in the sense transfectants, while the antisense transfected clones exhibited heterogeneous responses. The expression of the squamous differentiation markers cytokeratin K1, transglutaminase type I, and involucrin was increased in the absence of exogenous retinoid in a sense transfected clone and decreased in an antisense transfected clone. RA suppressed squamous differentiation in both types of transfectant. The expression of epidermal growth factor receptor (EGFR) was higher in the antisense and lower in the sense transfectant than in the parental cells and RA decreased EGFR mRNA level in the parental and the sense transfectant but not in the antisense transfectant. In addition activator protein-1 (AP-1) binding activity was decreased by the RA treatment in the sense clones, but not in the antisense ones. These results suggest that RARγ mediates the effects of RA on the cell growth both in monolayer culture and in semisolid medium possibly through AP-1 suppression.

Original languageEnglish (US)
Pages (from-to)2019-2028
Number of pages10
JournalOncogene
Volume12
Issue number9
StatePublished - Jun 3 1996
Externally publishedYes

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Keywords

  • Nuclear receptor
  • Retinoic acid
  • Retinoic acid receptor γ
  • Squamous differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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