Bone marrow stromal cell-derived growth inhibitor, BDGI, inhibits growth and migration of breast cancer cells via induction of cell cycle arrest and apoptosis
会议名称：《浙江省免疫学会第五次学术研讨会》
会议日期：2004年
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
摘 要：Genes encoding growth inhibitory proteins are postulated to be candidate tumor suppressors. The identification of such proteins may benefit the early diagnosis and therapy of tumors. Here we report the cloning and functional characterization of a novel human bone marrow stromal cell (BMSC)-derived growth inhibitor BDGI by large-scale random sequencing of a human BMSC cDNA library. Human BDGI cDNA encodes a 477-amino acid residue protein that shares high homology with rat and mouse pregnancy-induced growth inhibitors. The C-terminal of BDGI is identical to a novel human pregnancy-induced growth inhibitor, OKL38. BDGI is also closely related to many other eukaryotic proteins, which together form a novel and highly conserved family of BDGI-like proteins. BDGI overexpression inhibits the proliferation, decreases anchorage-dependent growth and reduces migration of MCF-7 human breast cancer cells, while down-regulation of BDGI expression promotes the proliferation of MCF-7 cells. Interestingly, the inhibitory effect of BDGI on MCF-7 cells is more potent than that of OKL38. We demonstrate that BDGI induces cell cycle arrest in S phase and subsequent apoptosis of MCF-7 cells, which is likely to account for BDGI’s anti-proliferative effects. This process may involve upregulation of p27kipl and downregulation of cyclin A, Bcl-2 and Bcl-xL. The inhibitory effect of BDGI on cell proliferation and the induction of apoptosis were also observed in A549 lung cancer cells but not HeLa cervix epitheloid carcinoma cells. These results indicate that BDGI might be a growth inhibitor for human tumor cells, especially breast cancer cells, possibly contributing to the development of new therapeutic strategies for breast cancer.