The role of ICT1 during MYC-deregulated fast-onset mouse plasmacytomagenesis
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Date
2016
Authors
Dahl, Amy Kathleen
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Abstract
Murine plasmacytoma models human cancers that involve deregulation of MYC. Overexpression and duplication of the immature colon carcinoma transcript 1 gene, Ict1, along with MYC deregulation may contribute to the aggressive mechanism for disease development in fast-onset mouse plasmacytomas. This study looks at Ict1 and c-MYC overexpression in mouse PreBmycER cells that serve as a cell culture model for MYC-dependent plasmacytomagenesis. An Ict1 inducible vector was transfected into the mouse PreBmycER cell line that contains inducible c-MYC. This allowed us to examine the effect of overexpression of ICT1 and c-MYC proteins simultaneously or each separately, on selected hallmark cancer cell traits such as increased proliferation, evasion of apoptosis and increased genomic instability. An increase in the number of cells in the S-phase was observed by 15 % and up to 20 % at 24 and 36 hours respectively, and cell doubling time shortened by almost 2 hours at 24 hours during peak ICT1 and c-MYC overexpression. Although, no noticeable change in apoptosis levels, or large scale genomic alterations were detected up to 96 hours post-ICT1 and c-MYC peak-overexpression, genomic instability was observed when MYC protein was overexpressed with or without ICT1 protein overexpression. Extrachromosomal elements increased in number and size during conditional MYC deregulation, and most of these elements (25 %) classified as Chromosome 11. These findings support Ict1 as a candidate gene that is selected for by MYC-deregulation during plasmacytomagenesis, and show promise that the experimental model of induced MYC and ICT1 overexpression in mouse PreB cells, deserves further investigation, specifically with in vivo studies.
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Keywords
Plasmacytoma, Myc, c-Myc, Ict1, Burkitt Lymphoma,