Retinoic acid and retinoid X receptors are differentially expressed in thyroid cancer and thyroid carcinoma cell lines and predict response to treatment with retinoids.
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 (RARalpha, -beta, -gamma and RXRalpha, -beta, -gamma) was measured in four human thyroid cell lines, and protein expression was subsequently measured in 10 thyroid cancer cell lines. Two isoforms, RARbeta and RXRgamma, were differentially expressed in the four cell lines. Comparison of 10 thyroid tumors and matched normal thyroid tissue confirmed differential tumor expression of RARbeta and RXRgamma and lack of the RXRgamma isoform in normal thyroid tissue. Cell lines expressing both RARbeta and RXRgamma demonstrated significant growth suppression when treated with retinoids, whereas cell lines lacking these isoforms were unaffected. Expression of RARbeta, 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 RARbeta and RXRgamma 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.
Haugen
Bryan R
BR
Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Larson
Lori Lee
LL
Pugazhenthi
Umarani
U
Hays
William R
WR
Klopper
Joshua P
JP
Kramer
Cynthia A
CA
Sharma
Vibha
V
D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D001565:Benzoates / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D047488:Retinoid X Receptors; D012176:Retinoids / Q000494:pharmacology / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000737:chemistry; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001565:Benzoates; D020033:Protein Isoforms; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid