Keywords
Akt1, twist1, emt, ovarian cancer
Abstract
Ovarian cancer results in more deaths per year than any other cancer of the female reproductive system. The low survival rate is partly due to the lack of early detection and the susceptibility to relapse. The AKT serine threonine kinase plays a pivotal role in hallmark cellular processes for the progression of ovarian cancer, including tumor cell growth and migration. Therapeutic targeting of pan-AKT has been problematic, in part due to feedback mechanisms and crosstalk with other pathways. The hypothesis for this study is that AKT 1, -2 and -3 isoforms may have different roles and regulate cell processes in uniquely varied ways. A transgenic mouse model that expresses the SV40 T-antigen viral oncogene and is known to have dramatically increased susceptibility to ovarian cancer was utilized, and it had genetic inactivation of either AKT1 or AKT2 through targeted deletion of the individual genes because these isoforms have been implicated in this cancer. Primary ovarian tumor cell cultures were established and found to exhibit different morphology, proliferation and migration that may indicate a different role for the AKT1 and AKT2 isoforms in these contexts. Ovarian tumor cells with absence of AKT1 predominantly exhibited reduced cell migration when compared to cells with retention of AKT1 and absence of AKT2. Since AKT is known to be important for epithelial-mesenchymal transition (EMT), a process potentially associated with tumor cell metastasis, the expression of transcription factors implicated in EMT was assessed by real-time array analysis in ovarian tumor cells knocked-out for either AKT1 or AKT2. Twist1, one of the major players in EMT, was not detectable in the cells missing the AKT1 isoform. Results indicate an association of Twist1 with AKT1 in EMT and migration of ovarian tumors cells. This finding is significant because AKT2 has been implicated as the major player of cell migration in human breast cancer iv cells. Collectively, these findings support a tissue specific role of the AKT isoforms, and may provide insights regarding the most useful cell context in order to target components of the AKT signaling pathway indirectly affecting EMT in order to prevent tumor progression in patients with ovarian and perhaps other types of cancers
Notes
If this is your thesis or dissertation, and want to learn how to access it or for more information about readership statistics, contact us at STARS@ucf.edu
Graduation Date
2012
Semester
Summer
Advisor
Altomare, Deborah
Degree
Master of Science (M.S.)
College
College of Medicine
Department
Molecular Biology and Microbiology
Degree Program
Biotechnology
Format
application/pdf
Identifier
CFE0004630
URL
http://purl.fcla.edu/fcla/etd/CFE0004630
Language
English
Release Date
February 2014
Length of Campus-only Access
1 year
Access Status
Masters Thesis (Open Access)
Subjects
Dissertations, Academic -- Medicine, Medicine -- Dissertations, Academic
STARS Citation
Shah, Nirav, "A Novel Link Between Akt1 And Twist1 In Ovarian Tumor Cell Motility And Invasiveness" (2012). Electronic Theses and Dissertations. 2297.
https://stars.library.ucf.edu/etd/2297