Disease relevance of Retinoic acid

• We show that it was rapidly induced in the acute promyelocytic leukemia (APL) cell line NB4 during granulocytic differentiation after exposure to retinoic acid (RA) [1].
• Retinoic acid (RA) induces cell cycle arrest and differentiation of human neuroblastoma (NB) cells [2].
• However, the relative induction of PEPCK gene expression by DEX, RA and cAMP, and its repression by INS, remained unaltered despite the substitution of the PEPCK TATA box with TATA elements from the herpes simplex virus-thymidine kinase gene, gene 33 or a consensus TATA box sequence, TATAAA [3].
• In THP-1 cells and in HL-60 human acute myelocytic leukemia cells, RA treatment increased the abundance of the 4.5-kb messenger RNA of the H2R gene fourfold, suggesting transcriptional control by a RA response element [4].

High impact information on Retinoic acid

• In retinoid-resistant APL cell lines, C/EBPepsilon either is not induced or is induced only at very high concentrations of RA (>/=10(-6) M) [1].
• PML/RARalpha, a repressor of RA target genes, abolished this UBE1L promoter activity [5].
• All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor alpha (RARalpha) [5].
• We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target [5].
• SH-F, which expresses basal amounts of p16(INK4A), responds to RA with elevation of p18(INK4C), marked down-regulation of cyclin D1, and swift inhibition of cyclin D-dependent kinases (cdks) [2].

Biological context of Retinoic acid

• We propose that rapid inhibition of cdks by RA in NB leads to early cell cycle arrest, prevents neuronal differentiation, and results in a senescence-like state [2].
• First, we show that the flattened RA-treated SH-F expresses markers of cells undergoing replicative senescence [2].
• Retinoic acid (RA) inhibits adipocyte differentiation of 3T3-L1 preadipocytes but is effective only early in adipogenesis [6].
• Although retinoic acid (RA) inhibits cell growth and induces differentiation in human APL cells, resistance to RA develops both in vitro and in patients [7].
• Retinoic acid (RA) induces growth arrest, cell death, and differentiation in many human cancer cells in vitro and has entered routine clinical use for the treatment of several human cancer types [8].

Anatomical context of Retinoic acid

• RA concentrations in human serum and in cancerous prostates were not significantly affected by 4-HPR treatment, in contrast with the findings in mice [9].
• RA-induced HL-60 cell differentiation and arrest in G0 was thus apparently not strongly dependent on cellular calmodulin levels or calcium flux [10].
• Treatment of cultured human keratinocytes with LPA or RA induced the production of TGF alpha by four- to eightfold [11].
• Two enzymes, NAD glycohydrolase and tissue transglutaminase, that are abundant in macrophages, were induced by RA but not by NAm [12].
• We have reported that retinol (R) and retinoic acid (RA) induced a down regulation of luteinizing hormone/human chorionic gonadotropin (LH/CG) binding sites in K9 Leydig cells [13].

Associations of Retinoic acid with other chemical compounds

• Epidermal ODC activity was also induced by topical 13-cis-RA, aromatic retinoid, and arotinoid ethyl ester at this time, although in lower amounts than after RA treatment [14].
• EBBP undergoes serine threonine phosphorylation and enhanced protein stability after RA treatment [8].
• The effects of LPA are compared with all-trans-retinoic acid (RA), a structurally unrelated lipid that has previously been shown to induce both TGF alpha and TGF beta and have pronounced effects on keratinocyte proliferation and differentiation [11].
• In this study, we analyzed the role of the TATA box in the regulation of the phosphoenolpyruvate carboxykinase (PEPCK) gene expression by dexamethasone (DEX), retinoic acid (RA), glucagon (via cAMP) and insulin (INS) [3].
• In a transgenic mouse model, a -460 and -355 bp PEPCK promoter fragment confers susceptibility to inhibition by vitamin A deficiency and responsiveness to all-trans RA treatment [15].

Gene context of Retinoic acid

• TGF-beta activity in the culture medium was also determined, finding that RA rapidly stimulates secretion of biologically active TGF-beta, the elevation being evident after 1 day of culture [16].
• Taken together, these results indicate that the PEPCK retinoic acid response element (RARE)1 is required for 9-cis RA induction-but not all-trans RA induction-of the PEPCK gene [15].
• Conversely, after addition of RA, SH-N retains cell cycling due to high expression of cyclin D1, the absence of Ink4 inhibitors, and accumulation of p21(Cip1) [2].
• The RA response element beta (betaRARE) is the essential DNA sequence required for retinoid-induced RARbeta transcription [8].
• RA treatment dramatically induced a DR5-binding RXRalpha-RARbeta heterodimer [17].

Analytical, diagnostic and therapeutic context of Retinoic acid

• RA induced epidermal ODC activity to levels only 15- to 30-fold less than found after treatment with the potent tumor promoter tetradecanoylphorbol-13-acetate [14].
• Cytosolic calmodulin levels were then measured as a function of cell cycle phase for RA-treated and untreated cells using a radioimmunoassay [10].

References