MED29, a component of the mediator complex, possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer.
MED29, a component of the mediator complex, possesses both oncogenic and tumor suppressive characteristics in pancreatic cancer.
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DOI：
10.1002/ijc.25924
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Kallioniemi, Anne
中科院分区：
文献类型：
--
作者：
Kuuselo, Riina;Savinainen, Kimmo;Sandstrom, Saana;Autio, Reija;Kallioniemi, Anne
介体复合物亚基29（MED 29）是一个大的多蛋白共激活因子复合物的一部分，介导调控信号从基因特异性激活剂的RNA聚合酶II介导的转录一般转录机制。我们先前发现MED 29在胰腺癌中扩增和过表达，并且MED 29沉默导致具有高MED 29表达的PANC-1胰腺癌细胞中细胞存活率降低。在这里，我们进一步证明了MED 29沉默后PANC-1细胞中迁移、侵袭和集落形成的减少。出乎意料的是，MED 29的基于慢病毒的过表达导致NIH/3 T3细胞以及具有低内源性表达的MIAPaCa-2胰腺癌细胞的增殖降低。更重要的是，将MED 29转导的胰腺癌细胞皮下接种到免疫受损的小鼠中导致了显著的肿瘤抑制。模拟对照小鼠产生了大肿瘤，而具有MED 29异种移植物的动物显示出肿瘤发生率降低和肿瘤大小的显著减小。MED 29转导的胰腺癌细胞中的基因表达分析揭示了参与细胞周期和细胞分裂控制的基因的差异表达。预期观察到的基因表达变化以导致细胞生长减少的方式调节细胞周期，从而解释体内肿瘤抑制表型。综上所述，这些数据表明MED 29是胰腺癌中关键细胞功能的重要调节因子，具有致癌和肿瘤抑制特征。这种双重作用似乎比以前认为的更常见，并且可能取决于癌细胞及其周围环境的遗传背景。
Mediator complex subunit 29 (MED29) is part of a large multiprotein coactivator complex that mediates regulatory signals from gene-specific activators to general transcription machinery in RNA polymerase II mediated transcription. We previously found that MED29 is amplified and overexpressed in pancreatic cancer and that MED29 silencing leads to decreased cell survival in PANC-1 pancreatic cancer cells with high MED29 expression. Here we further demonstrate decreased migration, invasion and colony formation in PANC-1 cells after MED29 silencing. Unexpectedly, lentiviral-based overexpression of MED29 led to decreased proliferation of NIH/3T3 cells as well as MIAPaCa-2 pancreatic cancer cells with low endogenous expression. More importantly, subcutaneous inoculation of the MED29-transduced pancreatic cancer cells into immuno-compromised mice resulted in dramatic tumor suppression. The mock-control mice developed large tumors, whereas the animals with MED29-xenografts showed both decreased tumor incidence and a major reduction in tumor size. Gene expression analysis in the MED29-transduced pancreatic cancer cells revealed differential expression of genes involved in control of cell cycle and cell division. The observed gene expression changes are expected to modulate the cell cycle in a way that leads to reduced cell growth, explaining the in vivo tumor suppressive phenotype. Taken together, these data implicate MED29 as an important regulator of key cellular functions in pancreatic cancer with both oncogenic and tumor suppressive characteristics. Such a dualistic role appears to be more common than previously thought and is likely to depend on the genetic background of the cancer cells and their surrounding environment.
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影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
9.7
作者：
Alarmo, Emma-Leena;Parssinen, Jenita;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne
影响因子：
11.2
作者：
Kuuselo, Riina;Savinainen, Kimmo;Kallioniemi, Anne
通讯作者：
Kallioniemi, Anne
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y