Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway

被引:137
作者
Kong, Lu [1 ,2 ]
Schaefer, Georg [1 ]
Bu, Huajie [1 ]
Zhang, Yong [3 ]
Zhang, Yuxiang [2 ]
Klocker, Helmut [1 ]
机构
[1] Innsbruck Med Univ, Div Expt Urol, Dept Urol, A-6020 Innsbruck, Austria
[2] Capital Med Univ, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China
[3] Capital Med Univ, Beijing Chao Yang Hosp, Dept Urol, Beijing 100043, Peoples R China
关键词
NUCLEAR LAMINS; GLEASON SCORE; RECENT TRENDS; EXPRESSION; MEN; PHOSPHORYLATION; ORGANIZATION; PROGNOSIS; AKT;
D O I
10.1093/carcin/bgs022
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prostate cancer (PC) remains the second most common cause of cancer-related death in Western countries. A previous proteomics study suggested that the nuclear membrane protein lamin A/C to be a maker to discriminate low- and high-Gleason score tumors and to identify high-risk cancers. To characterize its function in PC cells, we performed a detailed expression analysis in PC tissue and explored the consequences of down or upregulation of lamin A/C in PC cells. Our results confirm an increased lamin A/C protein expression in high-risk cancers and show association of expression with tumor cell formations at the invasion fronts of tumors and in invasion 'spearheading' tumor cell clusters. In the prostate tumor cell lines, LNCaP, DU145, and PC3 small hairpin RNA knockdown or overexpression of lamin A/C resulted in inhibition or stimulation, respectively, of cell growth, colony formation, migration and invasion. Further mechanism studies suggested that the lamin A/C-related malignant behavior is regulated through modulation of the phosphoinositide 3-kinase (PI3K)/AKT/PTEN signaling pathway. Western blot results indicated that knockdown or overexpression of lamin A/C decreased or increased, respectively, protein levels of the PI3K subunits p110 and p85 in all three cell lines; phosphor-AKT in the PTEN-negative cell lines LNCaP and PC3, and, increased or decreased, respectively, PTEN protein levels in PTEN-positive DU145 cells. Together, our data suggest that lamin A/C proteins are positively involved in malignant behavior of PC cells through the PI3K/AKT/PTEN pathway. Lamin A/C may represent a new oncogenic factor and a novel therapeutic target for PC.
引用
收藏
页码:751 / 759
页数:9
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