Stimulus-Selective Induction of CRABP-II mRNA: A Marker for Retinoic Acid Action in Human Skin

Elder, James T.; Cromie, Matthew A.; Griffiths, Christopher E.M.; Chambon, Pierre; Voorhees, John J.

doi:10.1111/1523-1747.ep12471816

Cited by 79 publications

(64 citation statements)

References 22 publications

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“…Gradual lowering of all-trans-RA concentration seems unlikely because of the low V value and relative short time of incubation. In contrast to what has been repeatedly described for the skin and for skin-derived cell cultures (Elder et al, 1993) Enzyme kinetic studies of all-trans-RA-induced all-trans-RA catabolism revealed an estimated Km value of 0.33 FiM. As a whole cell system is used, this estimated Km value reflects the uptake of all-trans-RA by the cells, the transport of all-trans-RA through the cells and the interactions of all-trans-RA with different cellular structures and organelles and serum present in the culture medium.…”

Section: Discussionmentioning

confidence: 56%

Induction of the oxidative catabolism of retinoic acid in MCF-7 cells

Krekels

Verhoeven²,

Dun³

et al. 1997

Br J Cancer

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Cytochrome P450-dependent oxidation is a pathway for all-trans-retinoic acid (all-trans-RA) catabolism. Induction of this catabolic pathway was studied in MCF-7 breast cancer cells. MCF-7 cells showed low constitutive all-trans-RA catabolism. Concentration-dependent induction was obtained by preincubation of the cells with all-trans-RA (10(-9) to 10(-6) M). Onset of induction was fast, being detectable within 60 min, with maximal induction (45-fold) obtained after 16 h. Enzymatic characterization of induced all-trans-RA catabolism showed an estimated Km value (Michaelis-Menten constant) of 0.33 microM and a Vmax value (maximal velocity of an enzyme-catalysed reaction) of 54.5 fmol polar all-trans-RA metabolites 10(6) cells(-1) h(-1). These kinetic parameters represent the overall formation of polar metabolites from all-trans-RA. Induction of all-trans-RA catabolism was also obtained with other retinoids, CH55 >> 13-cis-RA = all-trans-RA > 9-cis-RA > 4-keto-all-trans-RA > 4-keto-13-cis-RA > retinol. The potency of the retinoids to induce all-trans-RA catabolism was correlated to their retinoic acid receptor affinity (Crettaz et al, 1990; Repa et al, 1990; Sani et al, 1990). Induction of all-trans-RA catabolism was inhibited by actinomycin D. Furthermore, all-trans-RA did not increase cytosolic retinoic acid-binding protein (CRABP) mRNA levels. These data suggest that induction of all-trans-RA catabolism in MCF-7 cells is a retinoic acid receptor-mediated gene transcriptional event. Induced all-trans-RA catabolism was inhibited by various retinoids with decreasing potency in the order: all-trans-RA > 4-keto-all-trans-RA > 13-cis-RA > 9-cis-RA > 4-keto-13-cis-RA > retinol > CH55. The antitumoral compound liarozole-fumarate inhibited all-trans-RA catabolism with a potency similar to that of all-trans-RA. Images Figure 4

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Section: Discussionmentioning

confidence: 56%

Induction of the oxidative catabolism of retinoic acid in MCF-7 cells

Krekels

Verhoeven²,

Dun³

et al. 1997

Br J Cancer

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“…CRABPI and II are retinoic acid binding proteins that are known to have important functions within the skin (Elder et al, 1993). CRABPI is expressed in basal and suprabasal keratinocytes (Karlsson et al, 2002) and regulates retinoic acid degradation (Dong et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt

Janes

Ofstad

Campbell

et al. 2004

Journal of Cell Science

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The forkhead transcription factor FOXN1 is required for normal cutaneous and thymic epithelial development. Mutations in FOXN1 give rise to the nude phenotype in mice, rats and man. However, the genes that are regulated by FOXN1 are unknown. To investigate FOXN1 function we expressed an inducible form of the protein, FOXN1ER, that is activated by 4-hydroxytamoxifen in primary human epidermal keratinocytes. Transient activation of FOXN1 decreased the proportion of keratinocytes that formed actively growing clones attributable to stem cell founders and increased the number of abortive clones, without inducing apoptosis. Within 24 hours the majority of cells had initiated terminal differentiation, as assessed by involucrin expression. We performed a cDNA microarray experiment to analyse changes in the transcription of approximately 6000 genes. Following FOXN1 activation we detected increases of two fold or greater in the RNA levels of over 30 genes. Genes promoting growth arrest, survival and differentiation featured prominently and markers of early events in keratinocyte differentiation were also detected. Since one of the induced genes was Akt we investigated whether Akt played a role in terminal differentiation. Activation of PI 3-kinase but not Akt was necessary for FOXN1-induced differentiation. In reconstituted epidermis FOXN1 promoted early stages of terminal differentiation whereas Akt activation was sufficient to induce late stages, including formation of the cornified layers. These results establish a role for FOXN1 in initiation of terminal differentiation and implicate Akt in subsequent events.

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“…Epiluminescence microscopy (ELM) employs the oil immersion technique to render the epidermis translucent and the subsurface structures accessible to direct visualization [1, 2, 3, 4, 5, 6, 7, 8, 9]. Although preliminary observations have suggested that ELM can improve the clinical diagnosis of pigmented skin lesions, large-scale introduction of the technique into dermatology practice is considered premature [4, 6, 8].…”

Section: Introductionmentioning

confidence: 99%

Epiluminescence Microscopy versus Clinical Evaluation of Pigmented Skin Lesions: Effects of Operator’s Training on Reproducibility and Accuracy

Stanganelli

Bucchi

1998

Dermatology

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Background: An acceptable level of reliability is a prerequisite for the introduction of epiluminescence microscopy (ELM) into the diagnosis of pigmented skin lesions. Objective: To assess the effects of a training program on the reproducibility and accuracy of ELM as compared to clinical evaluation. Methods: Before and after the program, 48 clinical images and their ELM counterparts were independently evaluated by seven participants. Reproducibility was measured by the κ index, accuracy by the rate of exact diagnoses (RED) assuming histology as a reference. Results: We observed (i) no effect of training on clinical reproducibility, (II) an improved reproducibility of ELM diagnoses of nonmelanocytic lesions (NML) and melanomas but not of melanocytic nevi (MN), (iii) a greater increase in the clinical RED of NML and melanomas compared with MN and (iv) a similar though more pronounced increase in the RED on ELM. Conclusions: The effects of training were greater for ELM as compared to clinical diagnosis, and for NML and melanomas as compared to MN.

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Stimulus-Selective Induction of CRABP-II mRNA: A Marker for Retinoic Acid Action in Human Skin

Cited by 79 publications

References 22 publications

Induction of the oxidative catabolism of retinoic acid in MCF-7 cells

Induction of the oxidative catabolism of retinoic acid in MCF-7 cells

Transient activation of FOXN1 in keratinocytes induces a transcriptional programme that promotes terminal differentiation: contrasting roles of FOXN1 and Akt

Epiluminescence Microscopy versus Clinical Evaluation of Pigmented Skin Lesions: Effects of Operator’s Training on Reproducibility and Accuracy

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