Retinoid receptors in human breast carcinoma: Possible modulators of in situ estrogen metabolism

Retinoid receptors (retinoic acid (RARs) and retinoid X (RXRs) receptors) were immunolocalized in 32 human invasive ductal breast carcinomas. These findings were correlated with clinicopathological parameters to study their biological significance in breast carcinoma. Retinoid receptor immunoreactivity, except for RXRγ, was detected in the nuclei of carcinoma cells. Percentage of positive cases were RARα; 81%, RARβ; 6%, RARγ; 28%, RXRα; 81%, and RXRβ; 59%. A significant correlation was detected between RARα labeling index (LI), and RXRα LI (r = 0.667, p < 0.001). Results from immunoblotting performed in three cases were consistent with those of immunohistochemistry. There was a significant correlation between RARα LI and 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1 immunoreactivity (p < 0.05). A significant correlation was also detected between RARα (r = 0.413, p = 0.019) or RXRα (r = 0.429, p = 0.014) LI, and estrogen receptor (ER) LI. In T-47D breast cancer cells, which express RARα, RXRα and ER, 17β-HSD reductive activity increased 1.76-fold (p < 0.001), five days following treatment with 10 nM retinoic acid. These data suggest that retinoid receptors modulate various effects of retinoids, including estrogen metabolism in human breast carcinomas.