title: A novel cis-acting element in Her2 promoter regulated by Stat3 in mammary cancer cells.
abstract: Stat3 plays important roles in the development of breast malignancies and oncogenesis. In the present study, a palindromic cis-acting element displaying repression activity in breast cancer cells expressing low level of Her2 was found in Her2 promoter. Deletion analysis showed that the novel element was located within Pal2 region spanning nucleotides -529 to -505. The sequence analysis of Pal2 region revealed a DNA sequence (TTAAGATAA) homologous to the binding site of Stat3, starting from position -529 to -521bp. By reporter assay, Pal2 was found to be regulated by constitutive activated Stat3C. A stimulatory effect both on Her2 mRNA and protein expressions was observed in MCF-7 cells stably expressing Stat3C, suggesting that Stat3 regulated Her2 expression. Using ChIP assays the binding of Stat3 to Her2 promoter was confirmed. The data obtained in this study indicate constitutive activated Stat3 regulates Her2 expression. Further investigation of differential effects of Stat3 exerting on breast cancer cells expressing Her2 at different levels will provide more insights into the roles of Stat3 in Her2 expression as well as the regulation of diverse biological activities.
authors.affiliation: Institute of Basic Medical Sciences, Taiping Road 27, Beijing 100850, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Qian
authors.forename: Liyong
authors.initials: L
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Baofeng
authors.initials: B
authors.lastname: Jin
authors.forename: Meiru
authors.initials: M
authors.lastname: Hu
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhang
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D018734:Genes, erbB-2 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D046208:Microchip Analytical Procedures; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D050796:STAT3 Transcription Factor