Antagonistic Effects of Retinoic Acid and Hydrocortisone on Terminal Differentiation of Human Squamous Carcinoma Cells

Differentiation of SqCC/Y1, a juman malignant squamous carcinoma, can be modulated by the presence of both corticosteroids and retinoids. To evaluate the regulation of the differentiation of epidermal cells by these agents, we have employed delipidized serum from which glucocorticoids and retinoids...

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Bibliographic Details
Published in:Journal of investigative dermatology 1989-07, Vol.93 (1), p.165-168
Main Authors: Violette, Shelia M., King, Ivan, Sartorelli, Alan C.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - physiopathology
Cell Differentiation - drug effects
Dexamethasone - metabolism
Humans
Hydrocortisone - metabolism
Hydrocortisone - pharmacology
Medical sciences
Pharmacology. Drug treatments
Receptors, Glucocorticoid - metabolism
Skin, nail, hair, dermoskeleton
Tretinoin - pharmacology
Tumor Cells, Cultured
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Summary:Differentiation of SqCC/Y1, a juman malignant squamous carcinoma, can be modulated by the presence of both corticosteroids and retinoids. To evaluate the regulation of the differentiation of epidermal cells by these agents, we have employed delipidized serum from which glucocorticoids and retinoids were removed. Thirty percent of SqCC/Y1 cells spontaneously expressed the terminally differentiated phenotype after 6 d in culture, as measured by the capacity to form detergent-insoluble cornified envelops. Exposure of SqCC/Y1 cells to hydrocortisone at concentrations of 30, 100 and 300nM produced a 25, 100, and 175%, increase, respectively, in the number of differentiated cells over untreated control cultures. Exposure of cells to retinoic acid at levels of from 3 to 300nM caused a 24 to 85% decrease in the quantity of differentiated cells. Simultaneous treatment of SqCC/Y1 cells with hydrocortisone and retinoic acid resulted in mutual antagonism of cornified envelope formation. Treatment of SqCC/Y1 cells with a 1000-fold molar excess of retinoic acid did not directly alter the uptake of hydrocortisone, and a 100-fold molar excess did not directly inhibit the binding of the corticosteroid to its receptor. Pretreatment of cells for 48, 72, or 96h with 100nM retinoic acid decreased the binding of hydrocortisone ot its receptor by only 20%, and only resulted in a small decrease in the total amount of hydrocortisone associated with cells 48h after the addition of retinoic acid. These findings suggest that the antagonism between hydrocortisone and retinoic acid on the terminal differentiation of SqCC/Y1is not expressed at the level of the corticosteroid receptor.
ISSN:0022-202X
1523-1747
DOI:10.1111/1523-1747.ep12277393