Upregulation of TRAG3 gene in urothelial carcinoma of the bladder.
Upregulation of TRAG3 gene in urothelial carcinoma of the bladder.
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DOI：
10.1002/ijc.25631
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发表时间：
2011-06-15
影响因子：
6.4
通讯作者：
Hsieh, Jer-Tsong
中科院分区：
文献类型：
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作者：
Karam, Jose A.;Huang, Sandra;Fan, Jinhai;Stanfield, Jennifer;Schultz, Roger A.;Pong, Rey-Chen;Sun, Xiankai;Mason, Ralph P.;Xie, Xian-Jin;Niu, Gang;Chen, Xiaoyuan;Frenkel, Eugene P.;Sagalowsky, Arthur I.;Hsieh, Jer-Tsong
常规化疗通常用于晚期膀胱癌，具有适度的成功率和高发病率。确定耐药标志物将使临床医生能够针对特定患者群体进行治疗。T24-致瘤细胞系在裸鼠中原位生长，并使用生物发光成像和微计算机断层扫描进行监测，直到它们发生转移。然后从原代膀胱（T24-P）、肺（T24-L）和骨（T24-B）组织中产生稳定的亚系。染色体分析和DNA微阵列被用来表征这些亚系。使用qRT-PCR和免疫组织化学（IHC）进行验证。表观遗传修饰剂用于研究基因调控。MTT法检测细胞活力。染色体分析显示，与T24-P相比，转移细胞系中存在多种改变。DNA微阵列分析显示，紫杉醇耐药相关基因3（TRAG 3）基因是上调最多的基因。根据qRT-PCR和IHC，TRAG 3在T24-L和T24-B中显著高于T24-P。TRAG 3基因表达可能受DNA甲基化而非组蛋白乙酰化控制。有趣的是，T24-B和T24-L细胞比T24-P对用抗微管剂如多西他赛、紫杉醇和长春碱处理更耐药。与正常邻近组织相比，20%的≤ pT 2患者（n=10）和60%的≥ pT 3患者（n=20）的TRAG 3 mRNA表达较高（p=0.05）。此外，与≤ pT 2肿瘤相比，≥ pT 3肿瘤中的TRAG 3中位表达高6.7倍。了解TRAG 3表达的状态可以帮助临床医生为特定的患者群体定制治疗，这些患者可以从治疗中受益，同时将耐药肿瘤患者分配给新的实验性治疗。
Conventional chemotherapy is commonly used for advanced stages of bladder cancer with modest success and high morbidity. Identifying markers of resistance will allow clinicians to tailor treatment to a specific patient population. T24-tumorigenic cell line was grown orthotopically in nude mice and monitored using bioluminescence imaging and microcomputed tomography until they developed metastases. Stable sublines were then developed from primary bladder (T24-P), lung (T24-L) and bone (T24-B) tissues. Chromosomal analysis and DNA microarray were used to characterize these sublines. qRT-PCR and immunohistochemistry (IHC) were used for validation. Epigenetic modifiers were used to study gene regulation. The cell viability was quantified with MTT assay. Chromosomal analysis revealed multiple alterations in metastatic cell lines compared to T24-P. DNA microarray analysis showed that Taxol-Resistance-Associated-Gene-3 (TRAG3) gene was the most upregulated gene. From qRT-PCR and IHC, TRAG3 was significantly higher in T24-L and T24-B than T24-P. TRAG3 gene expression is likely controlled by DNA methylation, but not histone acetylation. Interestingly, T24-B and T24-L cells were more resistant than T24-P to treatment with anti-microtubule agents such as docetaxel, paclitaxel and vinblastine. TRAG3 mRNA expression was higher in 20% of patients with ≤pT2 (n=10) and 60% of patients with ≥pT3 (n=20) compared to normal adjacent tissue (p=0.05). In addition, the median TRAG3 expression was 6.7-fold higher in ≥pT3 tumors compared to ≤pT2 tumors. Knowing the status of TRAG3 expression could help clinicians tailor treatment to a particular patient population that could benefit from treatment, while allocating patients with resistant tumors to new experimental therapies.
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影响因子：
--
作者：
Yao, XM;Hu, JF;Hoffman, AR
通讯作者：
Hoffman, AR
影响因子：
3.5
作者：
Materna, Verena;Surowiak, Pawel;Lage, Hermann
通讯作者：
Lage, Hermann
影响因子：
6.4
作者：
Karam, Jose A.;Fan, Jinhai;Hsieh, Jer-Tsong
通讯作者：
Hsieh, Jer-Tsong
影响因子：
4.8
作者：
Chen, H;Toyooka, S;Hsieh, JT
通讯作者：
Hsieh, JT
DOI：
10.3816/clm.2007.n.003
发表时间：
2007-01-01
期刊：
CLINICAL LYMPHOMA & MYELOMA
影响因子：
--
作者：
Wu, Ka Lung;Beverloo, Berna;Sonneveld, Pieter
通讯作者：
Sonneveld, Pieter