Retinoic Acid Receptors and Cancers

Soprano, Dianne Robert; Qin, Pu; Soprano, Kenneth J.

doi:10.1146/annurev.nutr.24.012003.132407

Cited by 236 publications

(190 citation statements)

References 99 publications

(41 reference statements)

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“…Retinoid signals are transduced primarily through the ligand activation of two families of nuclear retinoid receptors: retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In the past two decades, RARβ has attracted much more attention due to findings of frequent loss of RARβ expression in various types of cancer including colon cancer, reduction of cell responsiveness to retinoid-mediated growth inhibition, or increase in the degree of tumorigenicity by knockdown RARβ gene or blockage of its expression using an antisense strategy [4,23]. Unlike 9-cis retinoic acid, ATRA only activates RARs, which makes it an ideal model for the study of retinoid resistance.…”

Section: Discussionmentioning

confidence: 99%

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Liu

Zheng

et al. 2010

Cellular and Molecular Biology Letters

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Abstract:Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE 2 production was measured with the ELISA assay. The expression of RARβ was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE 2 did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARβ in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE 2 did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARβ and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

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Section: Discussionmentioning

confidence: 99%

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Liu

Zheng

et al. 2010

Cellular and Molecular Biology Letters

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“…Retinoids are known to influence several biological processes such as growth, development, and differentiation [5,6]. The retinoid treatment is usually associated with induction of morphological changes and prolongation of doubling time [7]. This suppression of growth by retinoid treatment does not necessarily involve cell death but arrest the tumor cells in the G1 phase of the cell cycle [8].…”

Section: Introductionmentioning

confidence: 99%

N-(4-Hydroxyphenyl)retinamide induced differentiation with repression of telomerase and cell cycle to increase interferon-γ sensitivity for apoptosis in human glioblastoma cells

2008

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Glioblastoma is the most malignant and prevalent brain tumor in humans. It is composed of heterogenic abnormal astroglial cells that avoid differentiation, maintain proliferation, and reluctant to apoptosis. N-(4-Hydroxyphenyl) retinamide (4-HPR) induced astrocytic differentiation and increased sensitivity to interferon-gamma (IFN-γ) for apoptosis in human glioblastoma A172, LN18, and SNB19 cells. Combination of 4-HPR and IFN-γ significantly inhibited human telomerase reverse transcriptase (hTERT), cyclin dependent kinase 2 (CDK2), and survivin to upregulate caspase-8, caspase-9, and caspase-3 for increasing apoptosis in all glioblastoma cell lines. Hence, combination of 4-HPR and IFN-γ should be considered for controlling growth of different human glioblastoma cells.

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“…In hematopoietic progenitors, retinoids are powerful inducers of differentiation, particularly towards the neutrophil lineage (3,4). The biological functions of retinoids are mediated primarily through the retinoic acid receptors (RARs) that regulate the expression of multiple downstream target genes (5,6). RTP801 (also known as REDD1/Dig2/DDIT4) is a recently cloned gene that is induced at the transcriptional level in response to various stresses such as hypoxia, glucocorticoids and DNA damage (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

RTP801 is a novel retinoic acid–responsive gene associated with myeloid differentiation

Gery

Park

Vuong

et al. 2007

Experimental Hematology

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Objective-Retinoids are crucial in the regulation of fundamental cellular processes including terminal differentiation of both normal and malignant myeloid progenitors. The aim of this study was to identify and characterize retinoic acid (RA) target genes.Methods and Results-RTP801 is a recently cloned stress response gene that acts as a negative regulator of the mTOR pathway. Here we identified RTP801, as a novel early RA target gene in myeloid cells. RTP801 mRNA levels are induced in acute myeloid leukemia (AML) cell lines during RA-dependent differentiation and are differentially expressed during maturation of normal CD34 + cells. The myeloid specific, differentiation related transcription factor C/EBPε also induces RTP801 expression. Overexpression of RTP801 in the U937 leukemic cells leads to growth inhibition and apoptosis. Conversely, silencing of endogenous RTP801 by shRNA reduces RA-induced differentiation of the U937 cells. Downregulation of RTP801 also abrogates hypoxia-induced inhibition of mTOR in those cells.Conclusion-Taken together, our data suggest that RTP801 is an important RA regulated gene involved in myeloid differentiation, which could represent a therapeutic target in leukemia.

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Retinoic Acid Receptors and Cancers

Cited by 236 publications

References 99 publications

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

N-(4-Hydroxyphenyl)retinamide induced differentiation with repression of telomerase and cell cycle to increase interferon-γ sensitivity for apoptosis in human glioblastoma cells

RTP801 is a novel retinoic acid–responsive gene associated with myeloid differentiation

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