title: α-Synuclein expression selectively affects tumorigenesis in mice modeling Parkinson's disease.
abstract: Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-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 α-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 α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-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 α-Syn-dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over-expression of α-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 α-Syn may selectively accelerate cellular mechanisms leading to cancer.
authors: Department of Biochemistry and Molecular Biology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors: Eitan
authors: E
authors: Israeli
authors: Eugenia
authors: E
authors: Yakunin
authors: Yonaton
authors: Y
authors: Zarbiv
authors: Amir
authors: A
authors: Hacohen-Solovich
authors: Haya
authors: H
authors: Kisos
authors: Virginie
authors: V
authors: Loeb
authors: Michal
authors: M
authors: Lichtenstein
authors: Tziona
authors: T
authors: Ben-Gedalya
authors: Ofra
authors: O
authors: Sabag
authors: Eli
authors: E
authors: Pikarsky
authors: Haya
authors: H
authors: Lorberboum-Galski
authors: Ronit
authors: R
authors: Sharon
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