关键词：乳腺癌；转移；;基因表达；基因；医药
摘 要：The initial objective of this proposal is to characterize the regulation of BHC80 on the Snail-LSD1 interaction, and explore the prognostic value of BHC80 as biomarker for the metastasis of breast cancer. In the first year of the study, we aim to delineate the mechanisms underlying the interplay among BHC80, LSD1 and Snail. More specifically, we plan to verify if 1) the PHD finger of BHC80 interacts with the SNAG domain of Snail; 2) BHC80 affects the protein stability of Snail and LSD1; and 3) BHC80 affects LSD1/Snail binding to E-cadherin promoter. After we over-expressed the wild type and PHD finger deletion mutant of BHC80 in HEK293 cells and performed co-immunoprecipitation experiments, we found there was no significant difference between wild type and mutant BHC80 in regard to Snail binding affinity. We further identified that in addition to BHC80, PARP1 was a component of Snail/LSD1 complex. According to our initial data, BHC80 might cooperate with PARP1 to affect the protein stability of Snail and LSD1, as well as Snail/LSD1 binding to the target gene promoter. The identification and functional characterization of PAPR1 will potentially help us better understand the role of the Snail/LSD1 complex in breast cancer metastasis, and explore the prognostic value of this complex as a biomarker.