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Molecular Pharmacology

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Research ArticleArticle

Functional Consequences of Reduced Retinoic Acid Receptor γ Expression in a Human Squamous Cell Carcinoma Line

Ricardo I. Monzon, Catherine Fillmore and Laurie G. Hudson
Molecular Pharmacology March 1997, 51 (3) 377-382;
Ricardo I. Monzon
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Catherine Fillmore
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Laurie G. Hudson
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Abstract

Nuclear receptors for retinoic acid are important modulators of epidermal cell proliferation and terminal differentiation. Aberrant expression of retinoic acid receptors (RARs) and retinoid X receptors in the epidermis has been associated with altered differentiation capacity and tumor progression. In this study, we describe a human squamous cell carcinoma line, SCC 12F, which displays reduced RARγ expression and diminished responsiveness to retinoic acid. When compared with normal keratinocytes or other squamous cell carcinoma lines that display normal levels of RARγ, several measures of cellular response to retinoic acid are altered in SCC 12F cells, including inhibition of cornified envelope formation, reduction of involucrin mRNA expression, and transcriptional regulation of the involucrin gene. Normal patterns of ligand-dependent transcriptional response were restored upon co-transfection of an expression vector containing either RARα or RARγ. Our findings demonstrate that reduced expression of RAR may have direct functional consequences with regard to keratinocyte differentiation and that the defect may be alleviated by reintroduction of functional receptor.

Footnotes

  • Send reprint requests to: Dr. Laurie Hudson, Dept. of Molecular Pharmacology and Biological Chemistry, Searle 8–565, Northwestern University, 303 East Chicago Ave., Chicago, IL 60611.

  • This work was supported by American Cancer Society Grants BE-135 and JFRA-380 and in part by grant 0439 from the Smokeless Tobacco Research Council, Inc. R.I.M. is supported by National Institutes of Health training grant T32-ES07124–11.

  • Abbreviations:
    RAR
    retinoic acid receptor
    RXR
    retinoid X receptor
    DME
    Dulbecco’s modified Eagle’s medium
    F12
    Ham’s F12 nutrient mixture
    SCC
    squamous cell carcinoma
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    TPA
    12-O-tetradecanoylphorbol-13-acetate
    bp
    base pair(s)
    AP1
    activator protein 1
    • Received July 29, 1996.
    • Accepted December 6, 1996.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology
Vol. 51, Issue 3
1 Mar 1997
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Research ArticleArticle

Functional Consequences of Reduced Retinoic Acid Receptor γ Expression in a Human Squamous Cell Carcinoma Line

Ricardo I. Monzon, Catherine Fillmore and Laurie G. Hudson
Molecular Pharmacology March 1, 1997, 51 (3) 377-382;

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Research ArticleArticle

Functional Consequences of Reduced Retinoic Acid Receptor γ Expression in a Human Squamous Cell Carcinoma Line

Ricardo I. Monzon, Catherine Fillmore and Laurie G. Hudson
Molecular Pharmacology March 1, 1997, 51 (3) 377-382;
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