Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer.
Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor in thyroid cancer.
复制标题
DOI：
10.1186/1476-4598-13-62
复制
发表时间：
2014-03-19
期刊：
影响因子：
37.3
通讯作者：
Haugen BR
中科院分区：
文献类型：
--
作者：
Morrison JA;Pike LA;Sams SB;Sharma V;Zhou Q;Severson JJ;Tan AC;Wood WM;Haugen BR
甲状腺癌是最常见的内分泌恶性肿瘤，许多患有转移性分化型甲状腺癌（DTC）、低分化型甲状腺癌（PDTC）和间变性甲状腺癌（ATC）的患者对常规治疗无效，导致发病率和死亡率。这些患者需要额外的治疗靶点和治疗选择。我们最近报道了过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma，PPARγ）在ATC中高度表达，并且当在DTC细胞中过表达时赋予侵袭性表型。采用基因芯片技术鉴定ATC细胞中PPARγ的下游靶点。免疫印迹分析和免疫组织化学（IHC）被用来评估甲状腺癌细胞系和原发性肿瘤标本中硫氧还蛋白相互作用蛋白（TXNIP）的表达。逆转录病毒转导用于产生过表达TXNIP的ATC细胞系，并使用评估葡萄糖摄取、活细胞增殖和侵袭的测定来表征这些细胞的体外性质。原位甲状腺癌小鼠模型用于评估体内ATC细胞系中TXNIP过表达的作用。利用微阵列分析，我们表明，TXNIP是高度上调时，过氧化物酶体增殖物激活受体γ从ATC细胞耗尽。使用Western印迹分析和免疫组化，我们表明，DTC和ATC细胞表现出差异TXNIP表达模式。DTC细胞系和患者肿瘤具有高TXNIP表达，与ATC细胞系和肿瘤中的低表达或不表达相反。与载体对照相比，TXNIP的过表达降低了HTh 74细胞的生长，并抑制了ATC细胞系HTh 74和T238中的葡萄糖摄取。重要的是，在T238细胞中TXNIP过表达导致原位甲状腺癌小鼠模型中肿瘤生长减弱和转移减少。我们的研究结果表明，TXNIP在甲状腺细胞中起肿瘤抑制剂的作用，其下调可能在分化型甲状腺癌向晚期甲状腺癌的转变中起重要作用。这些研究强调了TXNIP作为晚期甲状腺癌新的治疗靶点和预后指标的潜力。
Thyroid cancer is the most common endocrine malignancy, and many patients with metastatic differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC), and anaplastic thyroid cancer (ATC) fail to respond to conventional therapies, resulting in morbidity and mortality. Additional therapeutic targets and treatment options are needed for these patients. We recently reported that peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ATC and confers an aggressive phenotype when overexpressed in DTC cells. Microarray analysis was used to identify downstream targets of PPARγ in ATC cells. Western blot analysis and immunohistochemistry (IHC) were used to assess thioredoxin interacting protein (TXNIP) expression in thyroid cancer cell lines and primary tumor specimens. Retroviral transduction was used to generate ATC cell lines that overexpress TXNIP, and assays that assess glucose uptake, viable cell proliferation, and invasion were used to characterize the in vitro properties of these cells. An orthotopic thyroid cancer mouse model was used to assess the effect of TXNIP overexpression in ATC cell lines in vivo. Using microarray analysis, we show that TXNIP is highly upregulated when PPARγ is depleted from ATC cells. Using Western blot analysis and IHC, we show that DTC and ATC cells exhibit differential TXNIP expression patterns. DTC cell lines and patient tumors have high TXNIP expression in contrast to low or absent expression in ATC cell lines and tumors. Overexpression of TXNIP decreases the growth of HTh74 cells compared to vector controls and inhibits glucose uptake in the ATC cell lines HTh74 and T238. Importantly, TXNIP overexpression in T238 cells results in attenuated tumor growth and decreased metastasis in an orthotopic thyroid cancer mouse model. Our findings indicate that TXNIP functions as a tumor suppressor in thyroid cells, and its downregulation is likely important in the transition from differentiated to advanced thyroid cancer. These studies underscore the potential of TXNIP as a novel therapeutic target and prognostic indicator in advanced thyroid cancer.
登录
查看更多内容
影响因子：
11.5
作者：
Kim, S;Park, YW;Myers, JN
通讯作者：
Myers, JN
影响因子：
11.2
作者：
Jeon, JH;Lee, KN;Choi, I
通讯作者：
Choi, I
影响因子：
11.2
作者：
Nishinaka, Y;Nishiyama, A;Yodoi, J
通讯作者：
Yodoi, J
DOI：
10.1158/1078-0432.ccr-11-3359
发表时间：
2012-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Chan CM;Jing X;Pike LA;Zhou Q;Lim DJ;Sams SB;Lund GS;Sharma V;Haugen BR;Schweppe RE
通讯作者：
Schweppe RE
DOI：
10.1186/bcr2599
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Cadenas C;Franckenstein D;Schmidt M;Gehrmann M;Hermes M;Geppert B;Schormann W;Maccoux LJ;Schug M;Schumann A;Wilhelm C;Freis E;Ickstadt K;Rahnenführer J;Baumbach JI;Sickmann A;Hengstler JG
通讯作者：
Hengstler JG