Abstract 1181: P73 regulates the expression of KAI1, metastasis suppressor gene

Abstract

Abstract KAI1, a metastasis suppressor gene of various cancers, has been known to inhibit tumor metastasis without affecting primary tumor growth. Identification of transcription factor regulating KAI1 is important for understanding tumor metastasis mechanism. P73 binding site within the KAI1 promoter were characterized by luciferase assay using reporter plasmids containing serial deletion promoter regions of KAI1 gene and chromatin-IP assay. To confirm whether the over-expressed KAI1 gene regulated by p73 in the transcriptional level was active, cell motility was analysed by using an adhesion and invasion assay. Here, we first identified that KAI1 is transcriptionally regulated by p73, a p53 family member, in various cancer cell lines. In p53-deficient cell lines, p73 had highest promoter binding activity in the KAI1 promoter regions between −903 and −846 bp, known as a p53-binding site. Human colon cancer cells stably overexpressing p73 showed that in vitro extracellular matrix adhesion and invasive potential was decreased compared with parental cells. These data explain that p73 regulate the KAI1 gene expression in the transcription level by binding on the specific region of the KAI1 promoter. In addition, it could be suggested that decreased invasion suppressive effect of KAI1 in invasive tumor and tumor cell lines caused by weak expression of KAI1 could be restored by increasing the p73 level. P73 might contribute the metastasis suppressive effect through upregulating KAI1 gene expression in invasive tumor and tumor cell lines. Taken together, our present results suggest that p73 contributes to KAI1 promoter activity in cells and plays an important role in the repression of tumor metastasis function via regulation of KAI1 expression in invasive tumor and tumor cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1181. doi:1538-7445.AM2012-1181