title: Regulation of vimentin gene transcription in human breast cancer cell lines.
abstract: We have investigated the control of vimentin expression in human breast cancer cell lines because of its transcriptional activation during malignant progression in breast cancer. Comparison of vimentin-positive (V+) and vimentin-negative (V-) breast cancer cell lines revealed several potential areas of vimentin gene regulation. Analysis of the chromatin structure of the vimentin gene in V+ and V- breast cancer cells showed DNase I hypersensitive sites in the 5' promoter region in V+ cell lines and 3' to the start of transcription in V- cell lines. Promoter deletion and reporter gene analysis revealed the importance of two adjacent AP-1 sites separated by seven GC-rich nucleotides for vimentin expression in V+ breast cancer cells. Mutational analysis of these sequences showed that although both AP-1 sites could bind nuclear proteins from V+ cells in vitro, one AP-1 site was sufficient to drive transcription in CAT reporter gene assays. The GC-rich spacer region had a modulating function on the activity of the AP-1 sites. In addition, levels of c-jun mRNA were elevated in V+ versus V- cells. In summary, distinct sites within the vimentin gene appear to be important for the control of vimentin expression in V+ and V- breast cancer cells with multiple elements acting coordinately to regulate vimentin expression.
authors.affiliation: Department of Medicine, Georgetown University School of Medicine, Washington, DC 20007.
authors.forename: C L
authors.initials: CL
authors.lastname: Sommers
authors.forename: J M
authors.initials: JM
authors.lastname: Skerker
authors.forename: S A
authors.initials: SA
authors.lastname: Chrysogelos
authors.forename: M
authors.initials: M
authors.lastname: Bosseler
authors.forename: E P
authors.initials: EP
authors.lastname: Gelmann
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002467:Cell Nucleus; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics*; D003850:Deoxyribonuclease I; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000235:genetics*
chemical_list: D018808:Transcription Factor AP-1; D014746:Vimentin; D015500:Chloramphenicol O-Acetyltransferase; D003850:Deoxyribonuclease I