α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease

被引:30
|
作者
Israeli, Eitan [1 ]
Yakunin, Eugenia [1 ]
Zarbiv, Yonaton [1 ]
Hacohen-Solovich, Amir [1 ]
Kisos, Haya [1 ]
Loeb, Virginie [1 ]
Lichtenstein, Michal [1 ]
Ben-Gedalya, Tziona
Sabag, Ofra [1 ]
Pikarsky, Eli
Lorberboum-Galski, Haya [1 ]
Sharon, Ronit [1 ]
机构
[1] Hebrew Univ Jerusalem, Hadassah Med Sch, IMRIC, Dept Biochem & Mol Biol, IL-91010 Jerusalem, Israel
来源
PLOS ONE | 2011年 / 6卷 / 05期
基金
美国国家卫生研究院;
关键词
BETA-SYNUCLEIN; GAMMA-SYNUCLEIN; CELL-DEATH; IN-VIVO; CANCER; RELEASE; GENE; OVEREXPRESSION; PROGRESSION; MECHANISMS;
D O I
10.1371/journal.pone.0019622
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Alpha Synuclein (alpha-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). alpha-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether alpha-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T alpha-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T alpha-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for alpha-Syn-dependent neurodegeneration. Importantly, transgenic alpha-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified alpha-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T alpha-Syn mice, over-expression of alpha-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of alpha-Syn may selectively accelerate cellular mechanisms leading to cancer.
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页数:9
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