The p44/wdr77-dependent cellular proliferation process during lung development is reactivated in lung cancer.
The p44/wdr77-dependent cellular proliferation process during lung development is reactivated in lung cancer.
复制标题
肺发育过程中 p44/wdr77 依赖性细胞增殖过程在肺癌中重新激活
DOI：
10.1038/onc.2012.207
复制
发表时间：
2013-04-11
期刊：
影响因子：
8
通讯作者：
Wang, Z.
中科院分区：
文献类型：
--
作者：
Gu, Z.;Zhang, F.;Wang, Z-Q;Ma, W.;Davis, R. E.;Wang, Z.
在肺发育过程中，细胞在开始分化之前增殖一段确定的时间。控制这种增殖过程的因素以及这种生长过程与肺癌的关系目前尚不清楚。在这里，我们发现WD 40蛋白（p44/wdr 77）在肺发育的早期阶段在生长的上皮细胞中表达。与此相反，p44/wdr 77的表达减少在完全分化的上皮细胞在成人肺。p44/wdr 77基因表达的缺失导致细胞生长停滞和分化。p44/wdr 77的重新表达导致终末分化的细胞重新进入细胞周期。我们的研究结果表明，p44/wdr 77是必不可少的，足够的肺上皮细胞的增殖。P44/Wdr 77在肺癌中重新表达，并且沉默p44/Wdr 77表达强烈抑制肺腺癌细胞在组织培养中的生长，并且消除小鼠肺腺癌肿瘤异种移植物的生长。p44/wdr 77表达缺失引起的生长停滞部分是通过p21-Rb信号传导。我们的研究结果表明，p44/wdr 77在肺发育过程中控制细胞增殖，并且这种生长过程在肺肿瘤发生过程中被重新激活。
During lung development, cells proliferate for a defined length of time before they begin to differentiate. Factors that control this proliferative process and how this growth process is related to lung cancer are currently unknown. Here, we found that the WD40-containing protein (p44/wdr77) was expressed in growing epithelial cells at the early stages of lung development. In contrast, p44/wdr77 expression was diminished in fully differentiated epithelial cells in the adult lung. Loss of p44/wdr77 gene expression led to cell growth arrest and differentiation. Re-expression of p44/wdr77 caused terminally differentiated cells to re-enter the cell cycle. Our findings suggest that p44/wdr77 is essential and sufficient for proliferation of lung epithelial cells. P44/Wdr77 was re-expressed in lung cancer, and silencing p44/wdr77 expression strongly inhibited growth of lung adenocarcinoma cells in tissue culture and abolished growth of lung adenocarcinoma tumor xenografts in mice. The growth arrest induced by loss of p44/wdr77 expression was partially through the p21–Rb signaling. Our results suggest that p44/wdr77 controls cellular proliferation during lung development, and this growth process is reactivated during lung tumorigenesis.
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DOI：
10.1073/pnas.88.12.5096
发表时间：
1991-06-01
影响因子：
11.1
作者：
JAT, PS;NOBLE, MD;KIOUSSIS, D
通讯作者：
KIOUSSIS, D
影响因子：
56.9
作者：
HALEVY, O;NOVITCH, BG;LASSAR, AB
通讯作者：
LASSAR, AB
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1158/1055-9965.epi-10-0565
发表时间：
2010-10
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Ma W;Wang M;Wang ZQ;Sun L;Graber D;Matthews J;Champlin R;Yi Q;Orlowski RZ;Kwak LW;Weber DM;Thomas SK;Shah J;Kornblau S;Davis RE
通讯作者：
Davis RE
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