Abstract 241: A novel function of thyroid hormone receptors in promoting metastasis of human hepatoma cells via regulation of TRAIL
| العنوان: | Abstract 241: A novel function of thyroid hormone receptors in promoting metastasis of human hepatoma cells via regulation of TRAIL |
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| المؤلفون: | Kwang-Huei Lin, I-Hsiao Chung, Chung-Ying Tsai, Hsiang-Cheng Chi, Yi-Hsin Tseng |
| المصدر: | Cancer Research. 72:241-241 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, medicine.medical_specialty, Thyroid hormone receptor, Biology, medicine.disease_cause, medicine.disease, Metastasis, Endocrinology, Oncology, Downregulation and upregulation, Tumor progression, Internal medicine, Cancer cell, medicine, Cancer research, Tumor necrosis factor alpha, Carcinogenesis, Receptor |
| الوصف: | Thyroid hormone (T3) and its binding receptors (TRs) are potent regulators mediating cell metabolism, proliferation, and differentiation. Accumulating evidence has confirmed an important role of TRs in tumor progression. However, the specific functions of TRs in carcinogenesis have yet to be clarified. Experiments from the present study have shown that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is upregulated by T3 in TR-overexpressing hepatoma cell lines. The T3-responsive element of the TRAIL promoter was localized to nucleotides at positions −1967 to −1977 upstream of the transcription start site. Interestingly, TRAIL acts as an apoptosis inducer in several cancer cell types, but also triggers non-apoptotic signals favoring tumorigenesis in apoptosis-resistant cancer cells. In our experiments, TR-overexpressing hepatoma cells treated with T3 were apoptosis-resistant, even under conditions where TRAIL was upregulated. This finding may be attributed to the simultaneous upregulation of Bcl-xL, an anti-apoptosis gene, by T3. Thus, overexpression of Bcl-xL in hepatoma cells possibly protects against apoptotic death triggered by TRAIL, consequently leading to TRAIL-promoted metastasis in hepatoma cells. Moreover, T3-enhanced metastasis was repressed by the treatment of TRAIL-blocking antibody. Notably, TRAIL was highly expressed in tumor cells of HCC patients, and this high expression was significantly correlated with the high TR expression as examined in 65 HCC tissues. Collectively, our findings indicate that TR directly binds to the TRAIL promoter to induce TRAIL expression, which acts in concert with the simultaneously activated anti-apoptotic factor, Bcl-xL, to promote metastasis, rather than apoptosis. Our findings provide a novel mechanistic link for increased TR and TRAIL in HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 241. doi:1538-7445.AM2012-241 |
| تدمد: | 1538-7445 0008-5472 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::fb6a5c9a65308a026980a7199ae481ebTest https://doi.org/10.1158/1538-7445.am2012-241Test |
| رقم الانضمام: | edsair.doi...........fb6a5c9a65308a026980a7199ae481eb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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