Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells.
Pim1 kinase is required to maintain tumorigenicity in MYC-expressing prostate cancer cells.
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DOI：
10.1038/onc.2011.371
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发表时间：
2012-04-05
期刊：
影响因子：
8
通讯作者：
Abdulkadir SA
中科院分区：
文献类型：
--
作者：
Wang J;Anderson PD;Luo W;Gius D;Roh M;Abdulkadir SA
PIM1激酶和MYC通常在人前列腺癌中共表达，并协同诱导小鼠模型中快速进展的前列腺癌。Pim激酶基因的缺陷在体内耐受性良好，表明PIM1抑制可能为前列腺癌，特别是MYC表达肿瘤提供有吸引力的治疗方式。在这里，我们研究了Pim 1和MYC在前列腺中过表达的分子后果，以及在具有高水平MYC的前列腺癌细胞中耗尽Pim 1的影响。Pim 1在小鼠前列腺中的过表达诱导了几种促肿瘤发生的遗传程序，包括细胞周期基因和Myc调节基因，然后诱导任何可辨别的病理学。在小鼠和人前列腺癌细胞中通过RNA干扰去除Pim 1降低了细胞增殖、存活、Erk信号传导和致瘤性，即使MYC水平没有显著改变。这些结果表明，PIM 1可能是必要的，以维持致瘤性，并进一步支持旨在开发PIM 1抑制剂用于前列腺癌治疗的努力。
PIM1 kinase and MYC are commonly co-expressed in human prostate cancer and synergize to induce rapidly progressing prostate cancer in mouse models. Deficiency of the Pim kinase genes is well tolerated in vivo, suggesting that PIM1 inhibition might offer an attractive therapeutic modality for prostate cancer, particularly for MYC-expressing tumors. Here we examine the molecular consequences of Pim1 and MYC over-expression in the prostate as well as the effects of depleting Pim1 in prostate carcinoma cells with high levels of MYC. Over-expression of Pim1 in the mouse prostate induces several pro-tumorigenic genetic programs including cell cycle genes and Myc-regulated genes prior to the induction of any discernible pathology. Pim1 depletion by RNA interference in mouse and human prostate cancer cells decreased cellular proliferation, survival, Erk signaling, and tumorigenicity even when MYC levels were not significantly altered. These results indicate that PIM1 may be necessary to maintain tumorigenicity, and further support efforts aimed at developing PIM1 inhibitors for prostate cancer therapy.