Abstract 2292: The role of immature colon carcinoma transcript 1 during c-myc deregulation in fast-onset mouse plasmacytoma

Murine plasmacytoma (mPCT) models human blood cancers that involve the deregulation of c-myc by a translocation that juxtaposes c-myc to one of the immunoglobin loci. The fast-developing mPCT does not depend on c-myc translocation; rather infection with v-abl/c-myc retrovirus produces elevated c-myc levels. Chromosome 11 subcytoband E2 is always (100%) found duplicated compared to slow-developing mPCT (7.1%). The gene, immature colon carcinoma transcript1 (ict1) is located within 11E2 and overexpressed as a result of 11E2 duplication. The effect of ict1 overexpression during c-myc deregulation may contribute to the aggressive development of mPCT. Here we look at the tumorigenic potential of ict1 in vitro. The ict1 gene has been cloned into an Ecdysone inducible vector and transiently transfected (Nucleofection) into mouse PreB cells that also have inducible c-myc expression activated by 4-hydroxytamoxifen. This allows us to look at overexpression of ict1 along with c-myc simultaneously or each separately. Immunofluorescence was used to confirm overexpression of the target genes. Proliferation and apoptosis levels were determined for each condition by Edu and TUNEL assay respectively. Metaphase spreads were prepared before and after each experiment. We have confirmed by immunofluorescence overexpression of ict1 using the inducible vector system. A study in these cell lines shows that ict1 overexpression increases cell proliferation levels, and may reduce apoptosis compared to cells that were not induced for ict1/c-myc expression. Metaphase spreads show normal diploid chromosome number of 40 (at time 0, and every 24 hours). Further genetic analysis to identify any chromosomal abnormalities that may account for these changes will be performed (SKY). We have identified a potential role of ict1 overexpression in vitro. In order to further explore these results we will try to restore proliferation and apoptotic levels relative to a normal PreB cell phenotype in plasmacytoma cells in vitro in the MOPC 460D cell line, and ex vivo in plasmacytoma cells isolated from PCT-carrying mice. 11E2 is syntenic to human chromosome 17q25, which has chromosomal abnormalities in many other neoplasms, such as acute and chronic myeloid leukemia, neuroblastoma, breast, ovarian, thyroid cancers. If we can identify the role of overexpression of ict1 during c-myc deregulation in fast-onset mPCT, we can gain insight into the aggressiveness of the disease progression and determine if i