α-synuclein expression selectively affects tumorigenesis in mice modeling parkinsons diseaseα-synuclein表达式有选择地影响肿瘤发生帕金森病小鼠模型.pdf

a-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson’s Disease 1¤ 1 1 1 1 Eitan Israeli , Eugenia Yakunin , Yonaton Zarbiv , Amir Hacohen-Solovich , Haya Kisos , Virginie 1 1 2 1 2 1 Loeb , Michal Lichtenstein , Tziona Ben-Gedalya , Ofra Sabag , Eli Pikarsky , Haya Lorberboum-Galski , Ronit Sharon1* 1 Department of Biochemistry and Molecular Biology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel, 2 Developmental Biology and Cancer Research, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel Abstract Alpha Synuclein (a-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson’s disease (PD). a-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 a-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 a-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T a-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 a-Syn- dependent neurodegeneration. Importantly, transgenic a-Syn