The tumor suppressor RASSF1A is required for mitotic commitment in cells

다국어 초록 (Multilingual Abstract)

RASSF1A(RAS association domain family protein 1A) is encoded by a putative tumor suppressor gene whose expression is frequently silenced in lung cancer and other sporadic cancers as a result of hypermethylation of a CpG island in its promoter. However, the mechanism by which RASSF1A might regulate cell growth has remained unknown. Here we demonstrate that RASSF1A both inhibits cell cycle progression at mitosis and promotes cell death when overexpressed in cancer cell lines. RASSF1A protein localizes to cytoplasmic microtubules during interphase and to spindle microtubules during mitosis. Cells overexpressing RASSF1A exhibit various mitosis-related abnormalities that result in mitotic arrest at prometaphase and aneuploidy. In addition, loss of RASSF1A expression in both cancer cell lines and primary human cells results in mitotic acceleration and chromosomal instability. These results suggest that RASSF1A regulates mitosis through its association with spindle microtubules and triggers apoptosis in cells with mitotic dysfunction. Loss of RASSF1A may thus contribute lung carcinogenesis by inducing chromosomal instability.