ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer.
ALKBH3, a human AlkB homologue, contributes to cell survival in human non-small-cell lung cancer.
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DOI：
10.1038/sj.bjc.6606012
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发表时间：
2011-02-15
影响因子：
8.8
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中科院分区：
文献类型：
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我们首次证明了一种新的人类AlkB同源物ALKBH 3有助于前列腺癌的发展，但其在肺癌中的临床和生物学作用仍不清楚。RT-PCR和Western blotting检测PCA-1 mRNA和蛋白的表达。我们还评估了原位肿瘤细胞接种与衰老和体内ALKBH 3治疗的相关性，并对其进行了临床病理学分析。此后，我们发现ALKBH 3在人类肺癌，特别是腺癌中的新生物学作用。我们对肺腺癌和鳞状细胞癌的免疫组化分析不仅显示ALKBH 3在这些肿瘤中过表达，而且ALKBH 3阳性细胞的百分比也与腺癌的无复发生存率统计学相关。通过siRNA转染ALKBH 3可诱导人肺腺癌细胞系A549中p21 WAF 1/Cip 1和p27 Kip 1的表达，导致细胞周期停滞、衰老和细胞生长的强烈抑制。在体内，通过腹膜内注射ALKBH 3 siRNA +去端肽胶原，在先前接种A549细胞系的裸鼠中抑制腹膜肿瘤生长和播散，如腹膜中发展的肿瘤数量和直径减少所证明的。我们认为ALKBH 3对癌细胞的存活有重要作用，可能是人类肺腺癌的治疗靶点。
We have demonstrated for the first time that a novel human AlkB homologue, ALKBH3, contributes to prostate cancer development, but its clinical and biological roles in lung cancer remain unclear. Expression of both mRNA and protein of PCA-1 was examined by RT–PCR and western blotting. We also assessed association with senescence and in vivo ALKBH3 treatment on orthotopic tumour cell inoculation, and analysed it clinicopathologically. We have since found novel biological roles for ALKBH3 in human lung cancers, particularly in adenocarcinoma. Our immunohistochemical analysis of human adenocarcinomas and squamous cell carcinomas of the lung not only showed overexpression of ALKBH3 in these tumours but the percentage of cells positive for ALKBH3 also correlated statistically to recurrence-free survival in adenocarcinoma. Knockdown of ALKBH3 by siRNA transfection induced expression of p21WAF1/Cip1 and p27Kip1 in the human lung adenocarcinoma cell line A549, resulting in cell cycle arrest, senescence and strong suppression of cell growth in vitro. In vivo, peritoneal tumour growth and dissemination was inhibited in nude mice, previously inoculated with the A549 cell line, by intraperitoneal injection of ALKBH3 siRNA + atelocollagen, as demonstrated by the reduction in both number and diameter of tumours developing in the peritoneum. We suggest that ALKBH3 contributes significantly to cancer cell survival and may be a therapeutic target for human adenocarcinoma of the lung.
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DOI：
10.1126/science.1151710
发表时间：
2007-11-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gerken T;Girard CA;Tung YC;Webby CJ;Saudek V;Hewitson KS;Yeo GS;McDonough MA;Cunliffe S;McNeill LA;Galvanovskis J;Rorsman P;Robins P;Prieur X;Coll AP;Ma M;Jovanovic Z;Farooqi IS;Sedgwick B;Barroso I;Lindahl T;Ponting CP;Ashcroft FM;O'Rahilly S;Schofield CJ
通讯作者：
Schofield CJ
DOI：
10.1073/pnas.97.8.4291
发表时间：
2000-04-11
影响因子：
11.1
作者：
Chang, BD;Watanabe, K;Roninson, IB
通讯作者：
Roninson, IB
影响因子：
8
作者：
Robles, SJ;Adami, GR
通讯作者：
Adami, GR
影响因子：
11.5
作者：
Massarelli, Erminia;Varella-Garcia, Marileila;Wistuba, Ignacio I.
通讯作者：
Wistuba, Ignacio I.
影响因子：
64.8
作者：
通讯作者：
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