Poster Sessions

CANCER-38

Scott Winter

S. Winter, L. Lukes, K. Hunter

Arid4b is a Potential Breast Cancer Progression Modifier Gene

Arid4b is a component of the mSin3 histone deacetylase complex that has a known role in breast cancer progression and is a candidate gene underlying a metastasis quantitative trait locus (QTL) peak we have identified on mouse chromosome 13. We generated stable breast cancer cell lines expressing either the AKR (highly metastatic strain) or DBA (low metastatic strain) allele of Arid4b, and orthotopically implanted these lines into the mammary fat pad of syngeneic host mice. Met-1 cells expressing the AKR allele of Arid4b formed larger primary tumors than those expressing the DBA allele. We were also able to detect lung surface metastases in the AKR cohort, but not in the DBA cohort. We are in the process of performing functional analyses to determine a mechanism of action whereby Arid4b polymorphisms might influence tumorigenesis and metastasis. Sequencing has revealed a high density of non-synonymous SNPs between the AKR and DBA alleles in exon 22, which encodes a C-terminal region of the Arid4b protein that is known to mediate interaction with the mSin3a HDAC complex. We are currently using co-IPs and proteomics strategies to identify proteins that bind differentially to the AKR or DBA Arid4b proteins.