Abstract 3509: Overexpression of 14-3-3γ contributes to chromosomal instability in human lung cancer

Abstract

Abstract Lung cancer is the most common cause of cancer-related deaths, and nearly all lung cancers exhibit genomic instability which results in an abnormal number of chromosomes known as aneuploidy. In many lung cancers, 14-3-3 proteins have been shown to be aberrantly activated or suppressed, which implies that these proteins have potential roles in tumorigenesis. Our lab has demonstrated that over expression of one 14-3-3 family member, 14-3-3γ, in a non-small cell lung cancer cell line leads to an increase in the number of cells that exhibit polyploidy, suggesting that this 14-3-3 protein can disrupt normal chromosome segregation. Additionally, overexpression of 14-3-3γ leads to atypical DNA replication and cell cycle progression. Further evaluation of the polyploid population induced by overexpressing 14-3-3γ revealed that a majority of the cells were multinucleated, often with two or more nuclei of unequal size and morphology. Live cell microscopy shows that this nonlinear marked increase in nuclear content is due to unequal distribution of DNA to the daughter cells upon cellular division, promoting chromosomal instability. Our data indicates that 14-3-3γ may play an important role in maintaining normal diploidy, but when overexpressed, as seen in many lung cancers, can lead to increased levels of chromosomal instability and progression into aneuploidy. Citation Format: Cecil J. Gomes, Sara Centuori, Jesse D. Martinez. Overexpression of 14-3-3γ contributes to chromosomal instability in human lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3509. doi:10.1158/1538-7445.AM2014-3509