Retinoic acid and retinoid X receptors are differentially expressed in thyroid cancer and thyroid carcinoma cell lines and predict response to treatment with retinoids
Retinoic acid and retinoid X receptors are differentially expressed in thyroid cancer and thyroid carcinoma cell lines and predict response to treatment with retinoids
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DOI：
10.1210/jc.2003-030770
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发表时间：
2004-01-01
影响因子：
5.8
通讯作者：
Sharma, V
中科院分区：
文献类型：
--
作者：
Haugen, BR;Larson, LL;Sharma, V
晚期甲状腺癌患者的治疗是有限的。临床和体外研究表明，一些晚期甲状腺癌患者可能对维甲酸治疗有反应。在4种人甲状腺细胞系中检测了6种视黄酸（RAR）和类视黄酸X受体（RXR）亚型（RAR α、- β、- γ和RXR α、- β、- γ）的mRNA表达，随后在10种甲状腺癌细胞中检测了蛋白表达。rrbeta和RXRgamma两种亚型在四种细胞系中有差异表达。将10个甲状腺肿瘤与匹配的正常甲状腺组织进行比较，证实了rrbeta和RXRgamma在正常甲状腺组织中的差异表达，以及RXRgamma亚型在正常甲状腺组织中的缺失。表达rbeta和RXRgamma的细胞系在类维生素a处理时表现出明显的生长抑制，而缺乏这些亚型的细胞系则不受影响。在甲状腺癌细胞系中，与抑制其他癌症类型肿瘤生长相关的rar β的表达不受类维生素a治疗的影响。LG346增加了间变性癌细胞s期细胞的凋亡，减少了细胞的凋亡，表明这种类维甲酸通过多种机制抑制了癌细胞的生长。总之，我们发现rrbeta和RXRgamma亚型在甲状腺癌细胞系和肿瘤组织中存在差异表达。这些异构体似乎可以预测甲状腺癌细胞系对类维甲酸治疗的反应。
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.