Prognostic value of the hDMP1-ARF-Hdm2-p53 pathway in breast cancer.
Prognostic value of the hDMP1-ARF-Hdm2-p53 pathway in breast cancer.
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DOI：
10.1038/onc.2012.423
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发表时间：
2013-08-29
期刊：
影响因子：
8
通讯作者：
Inoue, K.
中科院分区：
文献类型：
--
作者：
Maglic, D.;Zhu, S.;Fry, E. A.;Taneja, P.;Kai, F.;Kendig, R. D.;Sugiyama, T.;Miller, L. D.;Willingham, M. C.;Inoue, K.
我们最近的研究表明，Dmp1作为致癌Ras、HER2/neu信号传导和Arf-p53通路激活的传感器具有关键作用。为了阐明人DMP1 （hDMP1）在乳腺癌中的作用，我们研究了110对人乳腺癌标本中hDMP1- arf - hdm2 -p53通路的变化，并对临床结果进行了随访。在42%的人乳腺癌中发现hDMP1位点杂合性缺失（LOH），而INK4a/ARF和p53位点杂合性缺失分别在20%和34%的人乳腺癌中发现。在相同的样本中发现了13%的Hdm2扩增，这与hDMP1的LOH无关。相反，hDMP1的LOH与INK4a/ARF和p53的LOH相互排斥，并且与低Ki67指数和二倍体核型相关。一致地，hDMP1的LOH与腔内A类型和更长的无复发生存期相关，而p53的LOH与非腔内A和更短的生存期相关。因此，hDMP1的缺失可以定义一种与乳腺癌患者预后相关的新的疾病类别。携带野生型p53的人乳腺上皮细胞/癌细胞对激活的Dmp1:ER的生长抑制敏感，而删除p14ARF或p53和/或Hdm2扩增的细胞则表现出部分或近乎完全的抗性，这表明p53是hDMP1发挥其生物活性的关键靶点。
Our recent study showed critical roles of Dmp1 as a sensor of oncogenic Ras, HER2/neu signaling and activation of the Arf-p53 pathway. To elucidate the role of human DMP1 (hDMP1) in breast cancer, one hundred and ten pairs of human breast cancer specimen were studied for the alterations of the hDMP1-ARF-Hdm2-p53 pathway with follow up of clinical outcomes. Loss of heterozygosity (LOH) of the hDMP1 locus was found in 42% of human breast carcinomas, while that of INK4a/ARF and p53 were found in 20% and 34%, respectively. Hdm2 amplification was found in 13% of the same sample, which was found independently of LOH for hDMP1. Conversely, LOH for hDMP1 was found in mutually exclusive fashion with that of INK4a/ARF and p53, and was associated with low Ki67 index and diploid karyotype. Consistently, LOH for hDMP1 was associated with luminal A category and longer relapse-free survival, while that of p53 was associated with non-luminal A and shorter survival. Thus, loss of hDMP1 could define a new disease category associated with prognosis of breast cancer patients. Human breast epithelial cells/cancer cells with wild-type p53 were sensitive to growth inhibition by activated Dmp1:ER while those that delete p14ARF or p53, and/or Hdm2 amplification showed partial or nearly complete resistance, indicating that p53 is a critical target for hDMP1 to exhibit its biological activity.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
11.2
作者：
Frazier DP;Kendig RD;Kai F;Maglic D;Sugiyama T;Morgan RL;Fry EA;Lagedrost SJ;Sui G;Inoue K
通讯作者：
Inoue K
影响因子：
10.5
作者：
Inoue, K;Zindy, F;Sherr, CJ
通讯作者：
Sherr, CJ
影响因子：
11.5
作者：
Smeets, Serge J.;Harjes, Ulrike;Ylstra, Bauke
通讯作者：
Ylstra, Bauke
DOI：
10.1073/pnas.96.7.3993
发表时间：
1999-03-30
影响因子：
11.1
作者：
Inoue, K;Roussel, MF;Sherr, CJ
通讯作者：
Sherr, CJ