title: DNA Methylation Affects the SP1-regulated Transcription of FOXF2 in Breast Cancer Cells.
abstract: FOXF2 (forkhead box F2) is a mesenchyme-specific transcription factor that plays a critical role in tissue homeostasis through the maintenance of epithelial polarity. In a previous study, we demonstrated that FOXF2 is specifically expressed in basal-like breast cancer (BLBC) cells and functions as an epithelial-mesenchymal transition suppressor. FOXF2 deficiency enhances the metastatic ability of BLBC cells through activation of the epithelial-mesenchymal transition program, but reduces cell proliferation. In this study, we demonstrate that CpG island methylation of the FOXF2 proximal promoter region is involved in the regulatory mechanism of the subtype-specific expression of FOXF2 in breast cancer cells. DNMT1, DNMT3A, and DNMT3B commonly or individually contributed to this DNA methylation in different breast cancer cells. SP1 regulated the transcriptional activity of FOXF2 through direct binding to the proximal promoter region, whereas this binding was abrogated through DNA methylation. FOXF2 mediated the SP1-regulated suppression of progression and promotion of proliferation of non-methylated BLBC cells. Thus, we conclude that the subtype-specific expression and function of FOXF2 in breast cancer cells are regulated through the combined effects of DNA methylation and SP1 transcriptional regulation.
authors.affiliation: From the Department of Biochemistry and Molecular Biology and.
authors.forename: Hong-Pan
authors.initials: HP
authors.lastname: Tian
authors.affiliation: From the Department of Biochemistry and Molecular Biology and.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lun
authors.affiliation: From the Department of Biochemistry and Molecular Biology and.
authors.forename: Huan-Jing
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: From the Department of Biochemistry and Molecular Biology and.
authors.forename: Rui
authors.initials: R
authors.lastname: He
authors.affiliation: From the Department of Biochemistry and Molecular Biology and.
authors.forename: Peng-Zhou
authors.initials: PZ
authors.lastname: Kong
authors.affiliation: From the Department of Biochemistry and Molecular Biology and the Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Wang
authors.affiliation: From the Department of Biochemistry and Molecular Biology and the Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Li
authors.affiliation: From the Department of Biochemistry and Molecular Biology and the Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin 300060, China ymfeng@tijmu.edu.cn.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Feng
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002465:Cell Movement; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008969:Molecular Sequence Data; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology*; D015854:Up-Regulation
chemical_list: C486413:FOXF2 protein, human; D051858:Forkhead Transcription Factors; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human
keywords: DNA methylation; breast cancer; transcription factor; transcription target gene; transcriptional regulation