Seladin-1: A Novel Tumor Suppressor Gene Involved in Breast Cancer; Final rept. 17 Jul 2006-16 Jul 2008

摘要

Seladin-1 maps to the human chromosome region 1p31-1p32 that shows frequent loss of heterozygosity (LOH) in human breast tumors. Publicly available data (Entrez, GEO) also show a significant variability between levels of Seladin-1 expression in breast cancer cell lines and normal breast epithelium. Is Seladin-1 a tumor suppressor on 1p31 -1p32 that is involved in breast cancer. Our concept is that it is. In order to determine if Seladin-1 is a TSG involved in breast cancer we propose to: (1) Identify possible Seladin-1 mutations in primary breast tumors. (2) Investigate the alterations of Seladin-1 expression in breast cancer cells. (3) Perform functional assays on tumor- specific Seladin-1 mutants. Accordingly we amplified Seladin-1 exons from from 60 breast tumor genomic DNA samples (obtained from tissue banks or commercial sources) followed by the sequence analysis of the open reading frames. As a result no missense or nonsense mutations were detected. We found that expression of Seladin-1 significantly varies between different breast cancer cell lines and in one such line MDA-MB-231 is significantly below expression in normal breast epithelium.