Retinoids, Cancer, and the Skin

Elias, Peter M.; Williams, Mary L.

doi:10.1001/archderm.1981.01650030038018

Cited by 200 publications

(44 citation statements)

References 246 publications

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“…Morphologic studies indicate that vitamin A deficiency promotes the keratinization process characteristic of epidermis, whereas vitamin A excess promotes the differentiative processes typical of mucus-secreting or simple epithelia (Wolbach, 1954;Lotan, 1980;Wolf, 1980;Elias and Williams, 1981).…”

mentioning

confidence: 99%

Regulation of human mesothelial cell differentiation: opposing roles of retinoids and epidermal growth factor in the expression of intermediate filament proteins.

Kim

Stellmach

Javors

et al. 1987

The Journal of Cell Biology

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mentioning

confidence: 99%

Regulation of human mesothelial cell differentiation: opposing roles of retinoids and epidermal growth factor in the expression of intermediate filament proteins.

Kim

Stellmach

Javors

et al. 1987

The Journal of Cell Biology

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“…The basis for this potentiation of papilloma development is unknown. However, retinoic acid is a potent modulator of epithelial differentiation (37,38). This third point may have human health significance since a variety of agents capable of modulating epidermal differentiation are used topically in clinical and cosmetic applications.…”

Section: Discussionmentioning

confidence: 99%

Modulation of constitutive cytochrome P-450 expression in vivo and in vitro in murine keratinocytes as a function of differentiation and extracellular Ca2+ concentration.

Reiners

Cantu

Pavone

1990

Proc. Natl. Acad. Sci. U.S.A.

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A procedure was developed for the per cell estimation of cytochrome P-450-dependent monooxygenase activities in cultures and whole cell suspensions of murine epidermal keratinocytes (MEKs). Murine keratinocytes cultured in medium containing '0.04 mM Ca2l can be induced to differentiate by raising medium Ca2l concentrations to 1.2 mM. The per cell activities of the monooxygenases 7-ethoxyresorufin O-deethylase (7-ER) and 7-ethoxycoumarin O-deethylase (7-EC) were elevated .2090% and =460%, respectively, within 13-24 hr of Ca21 shift. These increases could be completely suppressed by supplementation of culture medium with actinomycin D or cycloheximiide immediately prior to Ca2+ shift. After prolonged culture in low Ca21 medium, some MEKs detached from the monolayer. These detached cells had the characteristics of differentiating MEKs but did not have elevated 7-EC or 7-ER activities. Percoll gradient centrifugation of freshly isolated dorsal skin MEKs was used to prepare four subpopulations that differed in their stages of terminal differentiation. 7-EC and 7-ER activities varied among these subpopulations and correlated with the degree of MEK differentiation. Specifically, the lowest and highest per cell activities (>7-fold difference) were in the basal and most differentiated spinous cell populations, respectively. Collectively, the current studies demonstrate that in vivo P-450 activities are markedly different in proliferating and differentiating MEKs and suggest that constitutive P-450 expression may be modulated as a function of changes in Ca2+ concentration that occur during keratinocyte terminal differentiation.The epidermis is not an impenetrable barrier. Many xenobiotics can be absorbed by the skin. In many cases the biological consequences of absorption are mediated by metabolites of the parent chemical. Numerous studies demonstrate that murine epidermis has the capacity to metabolize a variety of xenobiotics (1-4) and implicate the cytochrome P-450 system as the source of metabolism (4-8). However, biochemical characterization and quantitation of the epidermal P-450 system are rudimentary at best due to the extremely low levels of activity in the skin.Although the epidermis is principally composed of keratinocytes (9), there is considerable heterogeneity in the keratinocyte population due to the dynamic nature of skin differentiation. The specific activities of several epidermal enzymes vary with the stage of differentiation (10,11). The current study was designed to investigate whether cytochrome P-450 expression and content also vary as a function of the stage of keratinocyte differentiation. This study was stimulated by our recent demonstration of enhanced polycyclic aromatic hydrocarbon metabolism in cultures of differentiating mouse epidermal keratinocytes (MEKs) relative to proliferating MEKs (12). Kinetic analyses of hydrocarbon-dependent mutagenesis in the cultures led us to hypothesize that the differences in metabolism reflected the induction of enzymes capable of hydrocarbon metaboli...

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“…In skin cancer in mice, retinoic acid may inhibit the production of a key enzyme, ornithine decarboxylase, that enhances tumor promotion (8). Also, retinoids, by influencing the cell's protein synthesis, may directly compete for control of cell growth with agents that promote cancer (17,67). Also, retinoids can block the effects of transfonning growth factors that can cause cells to become cancerous (65).…”

Section: Vitamin a Beta-carotene Retinoidsmentioning

confidence: 99%

Diet and Chemoprevention in NCI's Research Strategy to Achieve National Cancer Control Objectives

Greenwald¹

1986

Annual Review of Public Health

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Retinoids, Cancer, and the Skin

Cited by 200 publications

References 246 publications

Regulation of human mesothelial cell differentiation: opposing roles of retinoids and epidermal growth factor in the expression of intermediate filament proteins.

Regulation of human mesothelial cell differentiation: opposing roles of retinoids and epidermal growth factor in the expression of intermediate filament proteins.

Modulation of constitutive cytochrome P-450 expression in vivo and in vitro in murine keratinocytes as a function of differentiation and extracellular Ca2+ concentration.

Diet and Chemoprevention in NCI's Research Strategy to Achieve National Cancer Control Objectives

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