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Functional retinoid and thyroid hormone receptors in human thyroid‐carcinoma cell lines and tissues
Author(s) -
Schmutzler Cornelia,
Brtko Julius,
Winzer Ralf,
Jakobs Tatjana C.,
MeissnerWeigl Jutta,
Simon Dietmar,
Goretzki Peter E.,
Köhrle Josef
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980504)76:3<368::aid-ijc14>3.0.co;2-7
Subject(s) - thyroid hormone receptor , thyroid hormone receptor beta , thyroid hormone receptor alpha , thyroid , thyroid carcinoma , nuclear receptor , cancer research , retinoic acid , retinoid x receptor , endocrinology , medicine , biology , cell culture , retinoid , electrophoretic mobility shift assay , thyroid cancer , receptor , microbiology and biotechnology , cancer , hormone receptor , gene expression , transcription factor , biochemistry , genetics , gene , breast cancer
Thyroid carcinomas no longer accessible to radio‐iodide or TSH‐suppressive T4 therapy, due to loss of thyroid‐specific functions, might be sufficiently re‐differentiated by retinoic acid (RA) to be treated by conventional methods again. To help evaluate the feasibility of RA re‐differentiation therapy in thyroid carcinomas, we examined the functionality of RA receptors (RARs/RXRs), central RA signal mediators, in human thyroid‐carcinoma cell lines as model systems. [ 3 H]‐RA binding assays with nuclear extracts from follicular thyroid‐carcinoma cell lines FTC‐133 and ‐238 revealed high‐affinity binding sites for RA. Electrophoretic mobility shift and supershift assays using a DR2 (“direct repeat” 2) RA response element demonstrated DNA‐binding of RARα, RARγ, RXRα and RXRβ in nuclear extracts of FTC‐133 and anaplastic HTh74 cells. Use of a DR5 RA response element revealed no difference in DNA binding. In supershift assays with a DR4 T3 response element, we found DNA‐binding by TRα1, TRα2, and TRβ. Northern‐blot analysis showed low expression of RXRβ mRNA in FTC‐133 and of TRα1 mRNA in FTC‐133 and FTC‐238 cells. Using RT‐PCR, we detected mRNA for RARα, RARβ, RARγ, RXRα, and RXRβ in the 4 cell lines and in human thyroid‐carcinoma samples. RARβ mRNA was reduced in FTC‐238 cells and RXRβ mRNA was decreased in anaplastic C643 cells and 9 of 12 tumor samples. Differential RA regulation of RA‐receptor‐mRNA expression was observed in the various cell lines. Thus, RA and T3 nuclear receptors are present in thyroid‐carcinoma cell lines or tissues, albeit with cell‐line and tumor‐dependent variations; in the cell lines, they were shown to be functional with respect to DNA and/or ligand binding. Int. J. Cancer 76:368–376, 1998.© 1998 Wiley‐Liss, Inc.