Related Experiment Video
Updated: Jun 25, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Antitumor effect of retinoic acid receptor-beta2 associated with suppression of cyclooxygenase-2
Shumei Song1, Baoxiang Guan, Taoyan Men
1Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:
Retinoic acid receptor-beta2 (RAR-beta2) is a putative tumor suppressor gene in various cancers. To determine the underlying molecular mechanisms, we transfected RAR-beta2 cDNA into esophageal cancer TE-1 and TE-8 cells and found that RAR-beta2 suppressed tumor cell growth in vitro and tumor formation in nude mice in TE-8 cells, whereas the stable transfection of RAR-beta2 did not restore retinoid sensitivity or inhibit tumor formation in nude mouse in TE-1 cells. Molecularly, we revealed that RAR-beta2 antitumor activity was associated with expression and suppression of cyclooxygenase-2 (COX-2) in these tumor cell lines. Moreover, antisense RAR-beta2 cDNA induced COX-2 expression in TE-3 cells. Furthermore, when COX-2 expression is first blocked by using antisense COX-2 expression vector, the effect of RAR-beta2 is diminished in these tumor cells. In addition, we analyzed expression of RAR-beta2 and COX-2 mRNA in tissue specimens and found that RAR-beta2 expression is associated with low levels of COX-2 expression in esophageal cancer tissues. Induction of RAR-beta2 expression in oral leukoplakia tissues after the patients treated with 13-cis RA correlated with a reduction in COX-2 expression and clinical response. Our findings indicate that some of RAR-beta2 antitumor activities are mediated by suppression of COX-2 expression in some of these esophageal cancer cells. After correlating antitumor effect of RAR-beta2 with COX-2 expression in the published studies, we also found the association. Thus, further studies will determine whether manipulation of COX-2 expression in different cancers can antagonize RAR-beta2 activity.
Insights
Retinoic acid receptor-beta2 (RAR-beta2) suppresses esophageal tumor growth by downregulating cyclooxygenase-2 (COX-2). This mechanism was observed in some cell lines and oral leukoplakia tissues, suggesting RAR-beta2
Area of Science:
- Molecular Oncology
- Cancer Biology
Background:
- Retinoic acid receptor-beta2 (RAR-beta2) is investigated as a potential tumor suppressor in various cancers.
- Understanding the molecular mechanisms of RAR-beta2's function is crucial for cancer therapy development.
Purpose of the Study:
- To investigate the role of RAR-beta2 in esophageal cancer.
- To elucidate the molecular mechanisms underlying RAR-beta2's antitumor activity, particularly its relationship with cyclooxygenase-2 (COX-2).
Main Methods:
- Transfection of RAR-beta2 cDNA into esophageal cancer cell lines (TE-1, TE-8).
- Assessment of tumor cell growth in vitro and tumor formation in nude mice.
- Analysis of RAR-beta2 and COX-2 mRNA expression in cell lines and patient tissue specimens.
- Inhibition of COX-2 expression using antisense vectors.
Main Results:
- RAR-beta2 suppressed tumor growth and formation in TE-8 cells but not TE-1 cells.
- RAR-beta2's antitumor activity correlated with the suppression of cyclooxygenase-2 (COX-2) expression.
- Antisense RAR-beta2 induced COX-2 expression, and blocking COX-2 diminished RAR-beta2's effect.
- RAR-beta2 expression was associated with low COX-2 levels in esophageal cancer tissues.
- RAR-beta2 induction in oral leukoplakia correlated with reduced COX-2 and clinical improvement.
Conclusions:
- RAR-beta2 exerts antitumor effects in some esophageal cancer cells, partly mediated by suppressing COX-2.
- The interplay between RAR-beta2 and COX-2 is a significant factor in esophageal tumorigenesis.
- Further research is warranted to explore targeting COX-2 to modulate RAR-beta2 activity in various cancers.
Related Concept Videos
Inhibition of Cdk Activity
Inhibition of CDK Activity
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...