Anti-TTK monoclonal antibody, clone Y2

Centrosome amplification (CA) amongst particular breast cancer subtypes (Her2+ subtype) is associated with genomic instability and aggressive tumor phenotypes. However, changes in signaling pathways associated with centrosome biology have not been fully explored in subtype specific models. Novel centrosome regulatory genes that are selectively altered in Her2+ breast cancer cells are of interest in discerning why CA is more prevalent in this subtype. To determine centrosome/cell cycle genes that are altered in Her2+ cells that display CA (HCC1954) versus non-tumorigenic cells (MCF10A), we carried out a gene microarray. Expression differences were validated by real-time PCR and Western blotting. After the microarray validation, we pursued a panel of upregulated and downregulated genes based on novelty/relevance to centrosome duplication. Functional experiments measuring CA and BrdU incorporation were completed after genetic manipulation of targets (TTK, SGOL1, MDM2 and SFRP1). Amongst genes that were downregulated in HCC1954 cells, knockdown of MDM2 and SFRP1 in MCF10A cells did not consistently induce CA or impaired BrdU incorporation. Conversely, amongst upregulated genes in HCC1954 cells, knockdown of SGOL1 and TTK decreased CA in breast cancer cells, while BrdU incorporation was only altered by SGOL1 knockdown. We also explored the Kaplan Meier Plot resource and noted that MDM2 and SFRP1 are positively associated with relapse free survival in all breast cancer subtypes, while TTK is negatively correlated with overall survival of Luminal A patients. Based on this functional screen, we conclude that SGOL1 and TTK are important modulators of centrosome function in a breast cancer specific model.

Despite the stated importance of a successful kindergarten transition (TTK) for future school success, no research has addressed this transition for culturally/ethnically diverse families having children with autism spectrum disorders (ASD). To address this gap, six focus groups (three with ethnically diverse parents, one with kindergarten teachers, and one each with early childhood resource teachers and early intervention providers) were conducted to elicit the experiences of these stakeholders regarding TTK for children with ASD generally, and the TTK experience for ethnically diverse families specifically. Four major themes relating to TTK emerged from the focus groups: Relationship Building, Communication, Knowledge, and Support. While these themes were relevant for all groups, parents who were relatively recent immigrants and for whom English was not a first language identified unique difficulties. Results are discussed within the context of Bronfenbrenner's Ecological Systems Theory. Recommendations to improve the experience for ethnically diverse families are explored.