S100A7, a member of S100 calcium binding protein family, is highly associated with breast cancer. However, the molecular mechanism of S100A7 regulation remains unclear. Here we show that long-term treatment with estradiol stimulated S100A7 expression in MCF7 breast cancer cells at both the transcriptional and translational levels. Both treatment with a histone demethylase LSD1 inhibitor and shRNA-based knockdown of LSD1 expression significantly decreased 17β-estradiol (E2)-induced S100A7 expression. These reduced E2-mediated S100A7 expression are rescued by the overexpressed wild-type LSD1 but not by its catalytically inactive mutant. Our data showed in vivo association of LSD1 with S100A7 promoters, confirming the potential role of LSD1 in regulating S100A7 expression. S100A7 knockdown increased both normal cell growth and estrogen-induced cell proliferation, suggesting a negative influence by S100A7 on the growth of cancer cells. Together, our data suggest that estrogen-induced S100A7 expression mediated by the histone demethylase LSD1 may downregulate breast cancer cell proliferation, implying a potential tumor suppressor-like function for S100A7.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2012 Oct 19|
Bibliographical noteFunding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korean Government ( KRF-2008-313-C00723 ). This study was supported in part by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (No. 0920260 ) to Y.K.J. In addition, this work was supported in part by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 20110030773 ) and partly by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2010-0010639 ). This work was supported in part by Mid-career Researcher Program through NRF grant funded by the MEST (No. 2009-0083772 ). S.E.Y. and Y.K.J. were supported by the Brain Korea21 (BK21) Program.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology