Abstract
Abstract Advanced non-small cell lung cancers (NSCLC), frequently display increased expression of 14-3-3 gamma (14-3-3γ); a scaffolding protein shown to have oncogenic capacity. This aberrant increase in expression has also been correlated with poorer survival, indicating that upregulation of 14-3-3γ results in a more aggressive tumor phenotype. Our lab is in pursuit of characterizing the mechanisms driving this more advanced cancer phenotype. One such mechanism currently being investigated is 14-3-3γ's ability to promote polyploidization in lung cancer cells. Polyploidization is a known mechanism observed to increase tumorigenicity, resistance to conventional therapies, and theorized to promote chromosomal instability. Our data shows that overexpression of 14-3-3γ results in a subpopulation of cells that harbor mono-nucleated tetraploid DNA content. This suggests that elevated expression of 14-3-3γ promotes aberrant cell cycle progression, either by mechanisms of an abortive mitosis known as endomitosis, or by means of endoreplication, a re-replication event occurring in the absence of mitosis. Further analyses have confirmed that these cells, in the absence of tumor suppressor p53, remain viable and undergo cellular division; supporting our hypothesis that upregulation of 14-3-3γ is resulting in an unstable, tumorigenic tetraploid cell state. Taken together, our data elucidates one role by which 14-3-3γ may be contributing to a more aggressive tumor phenotype in patients with advanced NSCLC. Citation Format: Cecil J. Gomes, Michael Harman, Jesse Martinez, Sara Centuori. Aberrant upregulation of 14-3-3 gamma promotes mononucleated polyploidization in human lung cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2066. doi:10.1158/1538-7445.AM2015-2066
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
