Novel Role of ANX7 in Breast Cancer Progression

摘要

The purpose of this study is to determine the mechanism and the signaling pathway by which the ANX7 gene induces death of breast cancer cells. The ANX7 induced apoptotic pathway involves calcium and cytochrome c release and morphological changes, nuclear fragmentation and chromatin condensation. Down-regulation of ANX7 in nude mice inhibited the tumors and metastasis by 50% in nude mice. Additionally, we confirmed the role of calcium by determining ANX7's control on all three subtypes of 1P3 Receptor expression. Overexpression of ANX7 reduces the percentage of cells that are capable of responding to the 1P3-generating agonist acetyicholine with a reduction in the magnitude of the response to acetylcholine. Using cDNA microarray and Western blot analysis, we have identified the downstream targets and signaling pathway of ANX7 in apoptosis and suppress ion of breast cancer cell growth. We confirmed the results that we obtained using cDNA microarray analysis, by promoter analysis and Western blot that TGF-beta1 is a downstream target for ANX7 and ANX7 activates TGF-beta1 through Smad signaling pathway regulated by calcium. These results not only establish the presence of a novel activation process following TGF-beta stimulation that requires calcium dependent ANX7-regulated activity, but also link two tumor suppressor pathways.