The role of PIM1/PIM2 kinases in tumors of the male reproductive system.

The role of PIM1/PIM2 kinases in tumors of the male reproductive system.
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DOI:
10.1038/srep38079
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发表时间:
2016-11-30
期刊:
影响因子:
4.6
通讯作者:
Carnero A
Carnero A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Jiménez-García MP;Lucena-Cacace A;Robles-Frías MJ;Narlik-Grassow M;Blanco-Aparicio C;Carnero A

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丝氨酸/苏氨酸激酶的PIM家族具有三种高度保守的同种型(PIM 1、PIM 2和PIM 3)。PIM蛋白通过JAK/STAT途径通过转录和稳定性进行调节,并且在血液恶性肿瘤和实体瘤中过表达。PIM激酶具有弱的致癌能力,但增强其他基因或化学致癌物诱导肿瘤。我们产生了在雄性生殖器官中过表达PIM 1或PIM 2的条件性转基因小鼠,并分析了它们对肿瘤发生的贡献。我们发现转基因小鼠的性器官改变和增生增加与炎症相关。我们还发现,PIM 1/2在人类男性生殖细胞和前列腺肿瘤中过表达,与炎症特征和干细胞标志物相关。我们的数据表明,PIM 1/2激酶过表达是男性生殖器官肿瘤的一个共同特征,它引起组织改变和大的炎症反应,可能在肿瘤发生过程中协同作用。还与癌症干细胞的标志物相关,这可能有助于在过表达PIM激酶的肿瘤中发现的治疗抗性。
The PIM family of serine/threonine kinases has three highly conserved isoforms (PIM1, PIM2 and PIM3). PIM proteins are regulated through transcription and stability by JAK/STAT pathways and are overexpressed in hematological malignancies and solid tumors. The PIM kinases possess weak oncogenic abilities, but enhance other genes or chemical carcinogens to induce tumors. We generated conditional transgenic mice that overexpress PIM1 or PIM2 in male reproductive organs and analyzed their contribution to tumorigenesis. We found an increase in alterations of sexual organs and hyperplasia in the transgenic mice correlating with inflammation. We also found that PIM1/2 are overexpressed in a subset of human male germ cells and prostate tumors correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression is a common feature of male reproductive organs tumors, which provoke tissue alterations and a large inflammatory response that may act synergistically during the process of tumorigenesis. There is also a correlation with markers of cancer stem cells, which may contribute to the therapy resistance found in tumors overexpressing PIM kinases.
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