Impaired Expression of Cytoplasmic Actins Leads to Chromosomal Instability of MDA-MB-231 Basal-Like Mammary Gland Cancer Cell Line

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (8), p.2151
• Main Authors: Dugina, Vera, Shagieva, Galina, Novikova, Mariya, Lavrushkina, Svetlana, Sokova, Olga, Kireev, Igor, Kopnin, Pavel
• Format: Article
• Language: English
• Subjects: Actin; actin isoforms; Actins - metabolism; Aneuploidy; Breast cancer; Cancer; Cell Cycle; Cell division; Cell Line, Tumor; Chromosomal Instability; chromosomal instability (CIN); Chromosomes; Cytoplasm - metabolism; Depletion; Down-Regulation; Endoreduplication; Female; Flow cytometry; Gene expression; Genomic instability; Genotype & phenotype; Humans; Isoforms; Karyotype; Karyotypes; Mammary gland; mammary gland cancer; Mammary glands; Mammary Glands, Human - metabolism; Mammary Glands, Human - pathology; Microscopy; Neoplasm Proteins - metabolism; Phenotype; Phenotypes; Phosphorylation; Polyploidy; Population; Protein Isoforms - metabolism; Proteins; RNA, Small Interfering - metabolism; Stability; Tumor cells; Tumor suppressor genes; Tumors; Visualization; Western blotting
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26082151

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.