Potential role of 5-aza-2'-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer.
Potential role of 5-aza-2'-deoxycytidine induced MAGE-A4 expression in immunotherapy for anaplastic thyroid cancer.
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DOI：
10.1016/j.surg.2013.07.009
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发表时间：
2013-12
期刊：
影响因子：
3.8
通讯作者：
Parangi, Sareh
中科院分区：
文献类型：
--
作者：
Gunda, Viswanath;Cogdill, Alexandria P.;Bernasconi, Maria J.;Wargo, Jennifer A.;Parangi, Sareh
MAGEA 4是癌症睾丸抗原（CTA）家族的成员，已在包括黑素瘤、膀胱、头颈部、口腔、肺的各种癌症中报道，并且是基于T细胞受体（TCR）的免疫疗法的潜在靶标。MAGEA 4基因在甲状腺癌细胞系中的基线表达水平以前没有被彻底研究过。用10μM 5-氮杂胞苷（Aza）、10μ M 5-氮杂-2-脱氧胞苷（DAC）处理人甲状腺癌细胞系（8505 c、HTh 7、BCPAP和TPC-1），并评价各种MAGEA基因表达。随后用PLX 4720与DAC组合处理黑素瘤细胞系A375和8505 c，并评价MAGEA 4表达。只有BCPAP细胞在基线时表达中等水平的MAGEA 3和A6。DAC/ Aza诱导8505 c细胞表达MAGEA 4和A1。PLX 4720处理不影响MAGEA 4在8505 c细胞中的表达，但增加其在A375细胞中的表达。然而，向DAC处理的8505 c细胞中添加PLX 4720降低了DAC在这些细胞中先前诱导的MAGEA 4表达。在8505 cBRAF −/−细胞中也观察到DAC对MAGEA 4表达的类似抑制。虽然DAC处理导致MAGEA 4启动子在两个CpG位点的去甲基化，但PLX添加到DAC中并不影响去甲基化状态。去甲基化剂可增加甲状腺癌细胞中法师的表达。BRAFV 600 E抑制剂对MAGEA 4表达的影响表明，除了启动子去甲基化是唯一的要求之外，下游MEK/BRAF信号传导在其表达中的作用。MAGEA 4的表达可能使特定甲状腺癌患者的免疫干预成为可能。
MAGEA4, a member of the cancer testis antigen (CTA) family has been reported in various cancers including melanoma, bladder, head and neck, oral, lung, and is a potential target for T cell receptor (TCR) based immunotherapy. Baseline expression levels of the MAGEA4 gene in thyroid cancer cell lines have not been previously thoroughly studied. Human thyroid cancer cell lines (8505c, HTh7, BCPAP and TPC-1) were treated with either 10μM 5’-azacytidine (Aza), 10μM 5-aza-2’deoxycytidine (DAC) and evaluated for various MAGEA gene expression. Later melanoma cell line, A375 and 8505c were treated with PLX4720 in combination with DAC and evaluated for MAGEA4 expression. Only BCPAP cells expressed moderate levels of MAGEA3 and A6 at baseline. Treatment with DAC/ Aza induced the expression of MAGEA4 and A1 in 8505c cells. PLX4720 treatment did not affect MAGEA4 expression in 8505c cells but increased its expression in A375 cells. However, addition of PLX4720 to DAC treated 8505c cells decreased the previously induced MAGEA4 expression by DAC in these cells. Similar dampening of MAGEA4 expression by DAC was also seen in 8505cBRAF−/− cells. While DAC treatment resulted in demethylation of the MAGEA4 promoter in two CpG sites, PLX addition to DAC did not affect the demethylation status. Demethylating agents increased the MAGE's expression in thyroid cancer cells. The effect of BRAFV600E inhibitors on MAGEA4 expression suggest the role of downstream MEK/BRAF signaling in its expression apart from promoter demethylation being the sole requirement. Expression of MAGEA4 may make immunotherapeutic intervention possible in selected thyroid cancer patients.
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DOI：
10.1634/theoncologist.2010-0317
发表时间：
2011
期刊：
The oncologist
影响因子：
--
作者：
Nucera C;Nehs MA;Nagarkatti SS;Sadow PM;Mekel M;Fischer AH;Lin PS;Bollag GE;Lawler J;Hodin RA;Parangi S
通讯作者：
Parangi S
影响因子：
7.4
作者：
Morse MA;Garst J;Osada T;Khan S;Hobeika A;Clay TM;Valente N;Shreeniwas R;Sutton MA;Delcayre A;Hsu DH;Le Pecq JB;Lyerly HK
通讯作者：
Lyerly HK
影响因子：
11.2
作者：
Nucera, Carmelo;Goldfarb, Melanie;Hodin, Richard;Parangi, Sareh
通讯作者：
Parangi, Sareh
影响因子：
5.8
作者：
Adair, Sara J.;Hogan, Kevin T.
通讯作者：
Hogan, Kevin T.
DOI：
10.1002/hed.21616
发表时间：
2011-10-01
影响因子：
2.9
作者：
Melo, Daniel Hardy;Martins Mamede, Rui Celso;Zago, Marco Antonio
通讯作者：
Zago, Marco Antonio