Disease relevance of Retinoic acid

• All of these properties are induced in undifferentiated embryonal carcinoma cells exposed to retinoic acid [1].
• Previous studies have shown that treatment of F9 teratocarcinoma cells with retinoic acid induces the expression of the classical transplantation antigens which are indispensable for effective interactions between cells [2].
• To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas [3].
• Consistent with this model, we find that HDAC inhibitors synergize with retinoic acid to stimulate hormone-responsive genes and differentiation of myeloid leukemia (HL-60) cells [4].
• To explore the generality of the effects of sarcoma viruses, tumor-promoting phorbol esters and retinoic acid, we have studied plasminogen activator production in differentiating chick myogenic cultures [5].

Psychiatry related information on Retinoic acid

• In the present study, we have determined the subcellular localization of SMN during retinoic-acid-induced neuronal differentiation of mouse embryonal teratocarcinoma P19 cells as well as in skeletal muscle during the critical period of neuromuscular maturation [6].
• Previous analyses of gene expression in a mouse model of Huntington's disease (R6/2) indicated that an N-terminal fragment of mutant huntingtin causes downregulation of striatal signaling genes and particularly those normally induced by cAMP and retinoic acid [7].
• The MMPI synthesized by retinol-treated EC was immunologically related to tissue inhibitor of metalloproteinases, type 1 (TIMP-1), and the MMPI produced by retinoic acid-treated cells was related to TIMP-2, as indicated by biosynthetic labeling and immunoprecipitation studies as well as Western blot analysis [8].
• To gain some insight into regulatory systems that might be operative during early human development, we have characterized the alterations that occur in the hormonal responsiveness of human embryonal carcinoma cell adenylate cyclase with differentiation in response to 10 microM retinoic acid [9].
• Retinoic acid decreased the latency period, reduced the probability that a mouse would survive without a tumor, and increased the number of tumors per mouse [10].

High impact information on Retinoic acid

• Finally, retinoic acid receptors regulate many developmental control genes, including homeobox genes and growth factor genes [11].
• The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling [12].
• The two factors compete for binding to the miR-223 promoter: NFI-A maintains miR-223 at low levels, whereas its replacement by C/EBPalpha, following retinoic acid (RA)-induced differentiation, upregulates miR-223 expression [13].
• Retinoic acid (RA) induces proliferation arrest, differentiation, and apoptosis, and defects in retinoic acid receptor (RAR) signaling have been implicated in cancer [12].
• Cyp26a1(-/-) mouse fetuses have lethal morphogenetic phenotypes mimicking those generated by excess retinoic acid administration, indicating that human CYP26A1 may be essential in controlling retinoic acid levels during development [14].

Chemical compound and disease context of Retinoic acid

• We investigated the treatment of this hyperpigmentation with topical tretinoin (0.1 percent retinoic acid cream) [15].
• Possible role of retinoic acid binding protein in retinoid stimulation of embryonal carcinoma cell differentiation [16].
• Treatment with retinoic acid (RA) and dibutyryl cyclic AMP can in some embryonal carcinoma (EC) cell lines lead to neural differentiation, as judged by neurofilament expression and by the induction of enzymes involved in cholinergic transmission [17].
• The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, involved in de novo cholesterol synthesis and cell-cycle progression, was identified as a potential mediator of the growth inhibitory effects of retinoic acid on human neuroblastoma [18].
• HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein-expressing cells [18].

Biological context of Retinoic acid

• These observations raise the intriguing possibility that coregulator proteins serve to restrict and/or direct the effects of retinoic acid receptors on patterns of gene expression during development [19].
• Analysis of the final phenotype indicates that it is not dependent upon the continued presence of either compound, and that cAMP agents are active only on cells that have been treated with retinoic acid [20].
• Several lines of evidence are presented for the existence of multiple, cell type-specific nuclear proteins that function to differentially increase the binding affinity of the alpha retinoic acid receptor for a variety of response elements [19].
• Promoter context- and response element-dependent specificity of the transcriptional activation and modulating functions of retinoic acid receptors [21].
• We have investigated the cell-specific activity of the GT-IIC, GT-I, Sph-II, Sph-I, and octamer motifs of the SV40 enhancer in four cell lines (HeLa cells, MPC11 plasmocytoma B cells, and non-differentiated and retinoic acid-differentiated F9 embryonal carcinoma cells) [22].

Anatomical context of Retinoic acid

• Upon differentiation of mouse teratocarcinoma cell line F9 with retinoic acid and cAMP, the expression of both genes was drastically reduced, and in one instance was undetectable [23].
• Plasminogen activator in chick fibroblasts: induction of synthesis by retinoic acid; synergism with viral transformation and phorbol ester [24].
• The induction of differentiation in teratocarcinoma stem cells by retinoic acid [25].
• When embryonal carcinoma cells are induced to differentiate by treatment with retinoic acid, diffusion constants of C16dil are reduced to levels typical of endoderm [26].
• To confirm their function, we implanted a bead containing retinoic acid, or the ZPA itself, in the anterior margin of the limb bud, leading to formation of mirror-image duplicated digits, and observed the resultant change in gene expression [27].

Associations of Retinoic acid with other chemical compounds

• Most of their actions are thought to result from changes in gene expression mediated by nuclear retinoic acid receptors and retinoid X receptors [28].
• This interaction results in a cooperative increase in binding of the alpha retinoic acid receptor to a subset of thyroid hormone response elements [29].
• When separated by 3 bp, direct repeat, palindromic, and inverted palindromic arrangements of these motifs impart selective transcriptional responses to retinoic acid, estrogen, and T3 receptors, respectively [30].
• We report here that v-erbA can actually interfere with the actions of a variety of members of the steroid/retinoid receptor family and that the ability of v-erbA to act in neoplasia best correlates not with suppression of c-erbA action, but with interference with the retinoic acid receptor response [31].
• The response to UV, TPA, or EPIF was inhibited by fluocinolone acetonide, but not by retinoic acid, protease inhibitors, or superoxide dismutase [32].

Gene context of Retinoic acid

• The aberrant PML-RAR fusion product, while typically retinoic acid responsive, displays both cell type- and promoter-specific differences from the wild-type RAR alpha [33].
• Acute promyelocytic leukaemia (APL) is uniquely associated with chromosomal translocations that disrupt the gene encoding the retinoic acid receptor, RARA [34].
• We provide genetic evidence that ALDH1A2 and CYP26A1 activities concurrently establish local embryonic retinoic acid levels that must be finely tuned to allow posterior organ development and to prevent spina bifida [14].
• Retinoic acid rescues inner ear defects in Hoxa1 deficient mice [35].
• The Cyp26a1 (cytochrome p450, 26) protein metabolizes retinoic acid into more polar hydroxylated and oxidized derivatives [14].

Analytical, diagnostic and therapeutic context of Retinoic acid

• We performed in situ hybridization of retinoic acid receptors and retinoid X receptors using antisense riboprobes in specimens of oral mucosa from 7 normal subjects and specimens of premalignant oral lesions from 52 patients before treatment with isotretinoin and from 39 of the 52 patients after three months of treatment [28].
• Differential formation of desmosomes and hemidesmosomes in epidermal cell cultures treated with retinoic acid [36].
• Retinoic acid (RA) has been shown to be effective in eradicating premalignant lesions and preventing second primary malignancies in patients cured of squamous cell carcinoma of the head and neck (SCCHN) in clinical trials [37].
• The phosphorylation of the serine residue at position 121 of ATF-2 appears to be induced by protein kinase C alpha (PKC alpha) after treatment of cells with retinoic acid (RA) or induction with E1A [38].
• Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis [39].

References