Schmutzler Cornelia, Hoang-Vu Cuong, Rüger Barbara, Köhrle Josef
Institut für Experimentelle Endokrinologie, Charité, Universitätsmedizin Berlin, Germany.
Eur J Endocrinol. 2004 Apr;150(4):547-56. doi: 10.1530/eje.0.1500547.
Disturbed expression of retinoic acid (RA) receptors (RAR/RXR) contributes to the pathogenesis and tumor progression of epithelial carcinomas.
To examine whether altered responses to retinoids may correlate with differences in RA receptor equipment, retinoid effects were examined in human thyroid carcinoma cell lines of various differentiation stages in culture and after xenotransplantation onto rodent models.
Cell growth was assessed by the MTT test, mRNA expression was examined by Northern blot and quantitative competitive RT-PCR, and type I 5'-deiodinase (5'DI) activity was measured by in vitro deiodination assay. Nude rats and mice were used for xenotransplantation experiments.
All-trans-RA and RAR-selective synthetic retinoids stimulated activity and mRNA expression of the thyroid differentiation marker 5'DI in the follicular thyroid carcinoma cell line FTC-133. In the less differentiated FTC-238 cells, stimulation of 5'DI activity was less pronounced than in FTC-133 cells, and a reduced level of RAR beta mRNA was detected. In the anaplastic thyroid carcinoma cell lines HTh 74 and C 643, the activity of 5'DI was not increased by retinoids, and expression of RAR alpha mRNA was reduced. Proliferation of FTC-133 and FTC-238 cells was decreased by all-trans-RA. Pretreatment of FTC-133 with RA resulted in a reduced tumor growth in xenotransplantation experiments as compared with untreated control cells. This reduction was less pronounced in the case of FTC-238 cells. Thus, retinoid therapy might be applied to treat follicular thyroid carcinomas. However, tumor-specific RAR repertoires need to be analyzed as a prerequisite for successful intervention with appropriate, probably receptor-selective retinoids.
维甲酸（RA）受体（RAR/RXR）表达紊乱与上皮癌的发病机制及肿瘤进展相关。
为研究对维甲酸反应的改变是否与RA受体装备的差异相关，在培养的不同分化阶段的人甲状腺癌细胞系以及异种移植到啮齿动物模型后，检测了维甲酸的作用。
通过MTT试验评估细胞生长，通过Northern印迹和定量竞争性RT-PCR检测mRNA表达，并通过体外脱碘测定法测量I型5'-脱碘酶（5'DI）活性。使用裸大鼠和小鼠进行异种移植实验。
全反式维甲酸和RAR选择性合成维甲酸刺激了滤泡状甲状腺癌细胞系FTC-133中甲状腺分化标志物5'DI的活性和mRNA表达。在分化程度较低的FTC-238细胞中，5'DI活性的刺激不如FTC-133细胞明显，并且检测到RARβmRNA水平降低。在间变性甲状腺癌细胞系HTh 74和C 643中，维甲酸未增加5'DI的活性，并且RARαmRNA的表达降低。全反式维甲酸降低了FTC-133和FTC-238细胞的增殖。与未处理的对照细胞相比，在异种移植实验中，用维甲酸预处理FTC-133导致肿瘤生长减少。在FTC-238细胞中，这种减少不太明显。因此，维甲酸疗法可能适用于治疗滤泡状甲状腺癌。然而，作为成功干预合适的、可能是受体选择性维甲酸的先决条件，需要分析肿瘤特异性RAR谱。
