Relationship between Retinoic Acid Receptor α Gene Expression and Growth‐Inhibitory Effect of All‐Trans Retinoic Acid on Canine Tumor Cells

Abstract

Retinoids show antitumor effects on human acute promyelocytic leukemia and other tumors via retinoid receptors. In dogs, the role of retinoid receptors in inhibiting tumor development remains unclear. To evaluate the correlation between the degree of expression of retinoic acid receptor α (RARα) mRNA and the antiproliferative effects of all‐trans retinoic acid (ATRA) treatments, expression analysis of RARα mRNA and cell growth inhibition assay were performed on 17 established canine tumor cell lines, including 6 mammary gland tumor (MGT) cell lines, 3 osteosarcoma cell lines, 5 melanoma cell lines, and 3 mast cell tumor (MCT) cell lines. Among the cell lines investigated, all 3 MCT cell lines showed high expression of RARα, and the most effective cell growth inhibition was observed in ATRA‐treated MCT cell lines. However, remarkable antiproliferative effects of ATRA treatments were not observed on other tumor cell lines with moderate or low RARα mRNA expression. As a result of the relationship between RARα mRNA expression and ATRA treatment with regression analysis, statistically significant correlation was suggested. Furthermore, real‐time quantitative polymerase chain reaction analysis of RARα was performed on MCT tissue samples of dogs with spontaneous disease, and 5 of 9 tissues showed high expression. These results suggest that ATRA may be an effective antitumor agent for MCT in dogs, and that prior measurement of expression of RARα: mRNA may be a good indicator of the effectiveness of ATRA treatment.