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Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line
Authors:Vera Dugina  Galina Shagieva  Mariya Novikova  Svetlana Lavrushkina  Olga Sokova  Igor Kireev  Pavel Kopnin
Institution:1.Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia; (V.D.); (G.S.); (S.L.); (I.K.);2.Biological Faculty, Lomonosov Moscow State University, 119234 Moscow, Russia;3.N.N. Blokhin National Medical Research Center of Oncology, 115478 Moscow, Russia; (M.N.); (O.S.)
Abstract:We have shown previously that two cytoplasmic actin isoforms play different roles in neoplastic cell transformation. Namely, β-cytoplasmic actin acts as a tumor suppressor, whereas γ-cytoplasmic actin enhances malignant features of tumor cells. The distinct participation of each cytoplasmic actin in the cell cycle driving was also observed. The goal of this study was to describe the diverse roles of cytoplasmic actins in the progression of chromosomal instability of MDA-MB-231 basal-like human carcinoma cell line. We performed traditional methods of chromosome visualization, as well as 3D-IF microscopy and western blotting for CENP-A detection/quantification, to investigate chromosome morphology. Downregulation of cytoplasmic actin isoforms alters the phenotype and karyotype of MDA-MB-231 breast cancer cells. Moreover, β-actin depletion leads to the progression of chromosomal instability with endoreduplication and aneuploidy increase. On the contrary, γ-actin downregulation results not only in reduced percentage of mitotic carcinoma cells, but leads to chromosome stability, reduced polyploidy, and aneuploidy.
Keywords:mammary gland cancer  actin isoforms  chromosomal instability (CIN)
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