Divergent impact of actin isoforms on cell cycle regulation

We have shown that cytoplasmic actin isoforms play different roles in neoplastic cell transformation. -Cytoplasmic actin acts as a tumor suppressor, affecting epithelial differentiation, cell growth, cell invasion and tumor growth of colon and lung carcinoma cells. In contrast, -cytoplasmic actin enhances malignant features of tumor cells whose actin network regulation is carried out via the -actin isoform. The goal of this study was to describe the role of cytoplasmic actins in cell cycle regulation of breast cancer cell lines MCF-7 and MDA-MB-231. The distinct roles of each cytoplasmic actin in the cell cycle driving were observed. -Actin as well as -actin down-regulation inhibited proliferation of breast cancer cells, but only down-regulation of -actin induced a significant decrease in diploid cell population and accumulation of tetraploid cells. Down-regulation of -actin stimulated cyclin A2, B1 and D3 expression, whereas down-regulation of -actin reduced expression of these cyclins in both cell lines. Moreover, cyclin B1 and -actin were co-localized in mitotic control and -actin-deficient cells. In mitotic MCF-7 cells down-regulation of -actin caused an enrichment of prophase/metaphase population compared with control. -Actin down-regulation induced telophase enrichment.ERK1/2 and -actin co-localization and possible selective binding were revealed in MCF7 cells. -Actin down-regulation induced ERK1/2 activation, while -actin down-regulation led to reduction of p-ERK1/2. A direct interaction of ERK1/2 with -actin and cyclin A2 in the same protein complex was also discovered. We suggest that -actin down-regulation leads to decrease of cyclin A2 level, inhibits ERK1/2 signaling and deceleration of breast cancer cells proliferation.