Poster abstracts

Poster number 81 submitted by Chaojie Wang

RCAN1-4 is a novel metastasis suppressor gene

Chaojie Wang (Ohio State Biochemistry Program), Adlina Mohd-Yusof (Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University), Samantha K. McCarty (Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University), Motoyasu Saji (Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University), Matthew D. Ringel (Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University)

Abstract:
Metastasis suppressor genes are those that inhibit metastasis and secondary progression whose loss can lead to metastatic progression. Defining their mechanisms of actions may yield critical findings that can lead to translational opportunities to improve treatment of progressive metastatic cancers. We recently identified RCAN1-4 (Regulator of Calcineurin 1-4) as a potential metastasis suppressor. Microarray analysis found that RCAN1-4 expression level was consistently upregulated in human thyroid cancer cells treated with metastin. In thyroid cancer tissues, metastatic lesions were shown to have much lower RCAN1-4 levels compared with paired primary tumors and in vitro studies showed RCAN1-4 suppressed cancer cell growth and motility. Other groups have shown that RCAN1-4 inhibits endothelial cell proliferation, migration, and angiogenesis in B16-F10 melanoma subcutaneous implants. Moreover, RCAN1, the gene from which RCAN1-4 and other splice variants are encoded, is partially responsible for the reduced solid tumor rate in Down syndrome, potentially through its effects on endothelial cells. Taken together, these data demonstrate that RCAN1-4 may function uniquely as a bona-fide tumor metastasis suppressor through effects on both tumor cells and the host. To determine its role in tumor cells in vivo, we have generated stable RCAN1-4 knockdown and inducible overexpression thyroid cancer cell lines, which will be used for xenograft studies to identify the role of RCAN1-4 in tumor cells during tumor progression. To determine the role of RCAN1-4 specifically in the host as a regulator of cancer progression, we have created a novel RCAN1-4 specific knockout mouse. These mice are viable and will be used to investigate the effects of RCAN1-4 knockout in the host on metastatic progression and tumor angiogenesis using syngenic model systems. Utilizing these systems, we anticipate being able to determine the mechanisms by which RCAN1-4 metastasis suppression occurs.

Keywords: RCAN1-4, Metastasis suppressor, Angiogenesis