Retinoic Acid and Retinoid X Receptors Are Differentially Expressed in Thyroid Cancer and Thyroid Carcinoma Cell Lines and Predict Response to Treatment with Retinoids

Abstract

Therapy for patients with advanced thyroid carcinoma is limited. Clinical and in vitro studies suggest that some patients with advanced thyroid cancer may respond to therapy with retinoic acid. mRNA expression of the six retinoic acid (RAR) and retinoid X receptor (RXR) isoforms (RARα, -β, -γ and RXRα, -β, -γ) was measured in four human thyroid cell lines, and protein expression was subsequently measured in 10 thyroid cancer cell lines. Two isoforms, RARβ and RXRγ, were differentially expressed in the four cell lines. Comparison of 10 thyroid tumors and matched normal thyroid tissue confirmed differential tumor expression of RARβ and RXRγ and lack of the RXRγ isoform in normal thyroid tissue. Cell lines expressing both RARβ and RXRγ demonstrated significant7 growth suppression when treated with retinoids, whereas cell lines lacking these isoforms were unaffected. Expression of RARβ, the isoform associated with suppression of tumor growth in other cancer types, was not affected by treatment with retinoids in the thyroid cancer cell lines. LG346 increased apoptosis and decreased cells in the S-phase in an anaplastic carcinoma cell line, suggesting that this retinoid causes growth suppression of these cells by multiple mechanisms. In summary, we identified the RARβ and RXRγ isoform to be differentially expressed in thyroid cancer cell lines and tumor tissue. These isoforms seem to predict response to retinoid therapy in thyroid cancer cell lines.