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

Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262

Address all correspondence and requests for reprints to: Bryan R. Haugen, M.D., Box B151, 4200 East Ninth Avenue, Denver, Colorado 80262. E-mail: bryan.haugen{at}uchsc.edu.

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 (RAR, -ß, - and RXR, -ß, -) was measured in four human thyroid cell lines, and protein expression was subsequently measured in 10 thyroid cancer cell lines. Two isoforms, RARß and RXR, were differentially expressed in the four cell lines. Comparison of 10 thyroid tumors and matched normal thyroid tissue confirmed differential tumor expression of RARß and RXR and lack of the RXR isoform in normal thyroid tissue. Cell lines expressing both RARß and RXR demonstrated significant growth suppression when treated with retinoids, whereas cell lines lacking these isoforms were unaffected. Expression of RARß, 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 RARß and RXR 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.

This work was supported by National Institutes of Health Grant DK 54383 and a grant from the Cancer League of Colorado.

Abbreviations: APL, Acute promyelocytic leukemia; 9-cis RA, 9-cis retinoic acid; DMSO, dimethylsulfoxide; FBS, fetal bovine serum; FNAB, fine-needle aspiration biopsy; HNSCC, head and neck squamous cell carcinoma; LBD, ligand-binding domain; RA, retinoic acid; RAR, RA isoform; RXR, retinoid X receptor isoform.

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