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Inhibition of all-trans retinoic acid on MDM2 gene expression in astrocytoma cell line SHG-44.

ABSTRACT: To investigate the impact of all-trans retinoic acid (ATRA) on MDM2 gene expression in astrocytoma cell line SHG-44, and to provide basic data for further research on the progression mechanism and gene therapy of human astrocytoma.The differential expressions of MDM2 gene and protein in SHG-44 cells were detected by cDNA microarray and Western blot, respectively, before and after treatment of ATRA. The expressions of MDM2 protein in WHO grade II and grade IV astrocytomas were determined by immunohistochemical streptavidin-peroxidase method. Some differentially expressed genes were selected randomly for Northern blot analysis.The intensity ratio of ATRA-treated to untreated SHG-44 cell was 0.37 in the cDNA microarray, suggesting that the expression of MDM2 gene was down-regulated in SHG-44 cells after treatment with ATRA. Some genes differentially expressed in the microarray were confirmed by Northern blot. Western blot demonstrated that the optical density ratios of MDM2 to beta-actin in ATRA-treated and untreated SHG-44 were 14.02+/-0.35 and 21.40+/-0.58 (t = 24.728, P = 0.000), respectively, suggesting that the expression of MDM2 protein was inhibited in ATRA-treated SHG-44 cells. Moreover, the percentages of MDM2-positive protein were 24.00% (6/25) and 56.52% (13/23) (chi(2) = 5.298, P = 0.021) in WHO grade II and grade IV astrocytomas, respectively, suggesting that the expression of MDM2 protein may increase along with the elevation of astrocytoma malignancy.ATRA can inhibit MDM2 gene expression in SHG-44 cells, and MDM2 is related to astrocytoma progression.

SUBMITTER: Zeng Y

PROVIDER: S-EPMC5552537 | biostudies-other | 2008 Oct

REPOSITORIES: biostudies-other

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G0S2 is an all-trans-retinoic acid target gene.

Project description:All-trans-retinoic acid (RA) treatment of acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, PML/RARalpha, is a successful example of differentiation therapy. Uncovering RA target genes is of considerable interest in APL. This study comprehensively examines in APL cells transcriptional and post-transcriptional regulation of the novel candidate RA target gene, G0S2, the G0/G1 switch gene. Reverse transcription (RT)-polymerase chain reaction (PCR) and heteronuclear PCR assays performed +/- treatment with the protein synthesis inhibitor cycloheximide (CHX) revealed G0S2 induction within 3 h of RA-treatment. Treatment with the RNA synthesis inhibitor actinomycin D did not implicate G0S2 transcript stabilization in the RA-mediated increase of G0S2 mRNA expression. Promoter elements of G0S2 were cloned into a reporter plasmid and retinoic acid receptor (RAR) co-transfection assays confirmed transcriptional activation after RA-treatment. Consistent with G0S2 being a direct RA target gene, retinoic acid response element (RARE) half-sites were found in this promoter. Mutation of these sites blocked RA-transcriptional activation of G0S2. To extend analyses to the protein expression level, a polyclonal anti-G0S2 antibody was derived and detected murine and human G0S2 species. G0S2 protein was rapidly induced in cultured NB4-S1 human APL cells and in APL transgenic mice treated with RA. An RAR pan-antagonist confirmed dependence on RARs for this induction. That these findings are clinically relevant was shown by analyses of APL cells derived directly from patients. These leukemic cells induced both a prominent increase in the cellular differentiation marker nitrotetrazolium blue (NBT) staining and marked increase in G0S2 expression. Taken together, these findings indicate G0S2 is an RA target gene. The functional role of G0S2 in retinoid response of APL warrants further study.

| S-EPMC2597086 | biostudies-literature

All-trans Retinoic Acid Counteracts Diarrhea and Inhibition of Downregulated in Adenoma Expression in Gut Inflammation.

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| S-EPMC7456978 | biostudies-literature

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| S-EPMC3322846 | biostudies-literature

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| S-EPMC1907337 | biostudies-literature

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| S-EPMC7465316 | biostudies-literature

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| S-EPMC4236914 | biostudies-literature

Polymer Nanoformulation of Sorafenib and All-Trans Retinoic Acid for Synergistic Inhibition of Thyroid Cancer.

Project description:Part of differentiated thyroid cancer will relapse or develop into dedifferentiated thyroid cancer after standard therapy, such as surgery or radionuclide therapy. Sorafenib (SOR) is recommended for the treatment of advanced or radioiodine-refractory thyroid cancer. The monotherapy using SOR is often hampered by its modest efficacy, serve systemic toxicity, and high occurrence of drug resistance. In order to enhance the antitumor effect of SOR and reduce its side effects, SOR and all-trans retinoic acid (ATRA), a differentiation-promoting drug, were loaded into poly(ethylene glycol)-poly(lactide-co-glycolide) (PEG-PLGA) polymer micelles in this study. The drug-loaded micelles, PM/(SOR+ATRA), exhibited relatively slow drug release and effective cell uptake. Compared with other treatment groups, the PM/(SOR+ATRA) treatment group showed the most significant antitumor effect and minimal systemic toxicity toward the FTC-133 thyroid cancer-bearing BALB/c nude mouse model. Immunofluorescence analysis confirmed that PM/(SOR+ATRA) could significantly promote apoptosis and re-differentiation of tumor cells. All the results demonstrated that polymer micelles loaded with SOR and ATRA could treat thyroid cancer more effectively and safely.

| S-EPMC7008594 | biostudies-literature

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Project description:DUOX1 and DUOX2 are members of the NADPH oxidase family that are specifically regulated to produce hydrogen peroxide in epithelia of the thyroid, gastrointestinal tract, and respiratory tract. The determinants of DUOX1 or DUOX2 expression in various tissues have not been established. Using respiratory tract epithelial cells as a model, we investigated changes in DUOX mRNA and protein expression during the first 10 days of differentiation. By comparing a respiratory tract cell line, HBE1, with primary tracheobronchial epithelial (TBE) cells, we determined that DUOX2 was significantly expressed only in cell conditions that included all-trans retinoic acid (ATRA). In HBE1 cells, DUOX2 mRNA increased 6-fold after ATRA treatment. Similarly, ATRA induced a 19-fold increase in DUOX2 mRNA expression in primary TBE cells with parallel increases in DUOX protein and DUOX-mediated H(2)O(2) production as well. In addition, DUOX2 induction by rhinovirus required the presence of ATRA. ATRA had no effect on DUOX1 expression for all the conditions studied. Our data indicate that for respiratory epithelial cells, ATRA is important in the regulation of DUOX2 expression, function, and rhinovirus-mediated DUOX2 inducibility.

| S-EPMC2928607 | biostudies-literature

Clinical Trial of All-trans-retinoic Acid, Bevacizumab and Atezolizumab in Colorectal Cancer

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| 70824 | ecrin-mdr-crc

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