JNK 和 PTEN 协同控制前列腺浸润性腺癌的发展。
JNK and PTEN cooperatively control the development of invasive adenocarcinoma of the prostate.
机构信息
University of Massachusetts Medical School, Worcester, MA 01605, USA.
出版信息
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12046-51. doi: 10.1073/pnas.1209660109. Epub 2012 Jul 2.
Abstract
The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (ΔJnk ΔPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (ΔPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (ΔMkk4 ΔMkk7 ΔPten mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an androgen-independent expansion of the immature progenitor cell population in the primary tumor. The JNK-deficient progenitor cells display increased proliferation and tumorigenic potential compared with progenitor cells from control prostate tumors. These data demonstrate that the JNK and PTEN signaling pathways can cooperate to regulate the progression of prostate neoplasia to invasive adenocarcinoma.
摘要
c-Jun NH(2)-末端激酶（JNK）信号转导通路与癌症有关，但 JNK 在肿瘤发生中的作用尚不清楚。在这里，我们证明 JNK 信号通路可降低磷酸酶和张力蛋白同源物（Pten）条件性缺失模型中前列腺癌的侵袭性腺癌的发展。前列腺上皮中 JNK 缺陷（ΔJnk ΔPten 小鼠）的小鼠比对照（ΔPten）小鼠更快地发展为雄激素非依赖性转移性前列腺癌。同样，预防前列腺上皮中的 JNK 激活（ΔMkk4 ΔMkk7 ΔPten 小鼠）会导致侵袭性腺癌的快速发展。我们发现，JNK 信号缺陷导致原发性肿瘤中不成熟祖细胞群体的雄激素非依赖性扩增。与来自对照前列腺肿瘤的祖细胞相比，JNK 缺陷的祖细胞显示出增加的增殖和致瘤潜能。这些数据表明，JNK 和 PTEN 信号通路可以合作调节前列腺肿瘤向侵袭性腺癌的进展。
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