title: SET domain-containing Protein 4 (SETD4) is a Newly Identified Cytosolic and Nuclear Lysine Methyltransferase involved in Breast Cancer Cell Proliferation.
abstract: Cancer is comprised of a multitude of epigenetic abnormalities, including the global loss and regional gain of DNA methylation as well as alterations in histone methylation. Here, we characterize a new methyltransferase, SET domain-containing protein 4 (SETD4), which is involved in breast carcinogenesis. Quantitative real-time PCR (qPCR) showed elevated expression levels of SETD4 in several breast cancer cell lines. SETD4 overexpression was confirmed by western blot analysis suggesting a correlation between high expression of SETD4 and a lack of the estrogen receptor (ER) in breast cancer. In addition, cell fractionation studies and confocal immunofluorescence revealed the nuclear and non-nuclear localization of this new protein. SETD4 knockdown in breast cancer cell lines significantly suppressed their proliferation and delayed the G1/S cell cycle transition without affecting apoptosis. Furthermore, western blot analysis showed that knockdown of SETD4 decreased cyclin D1 expression, revealing the involvement of SETD4 in cell cycle regulation. These data imply that SETD4 plays a crucial role in breast carcinogenesis and could be a novel molecular target for the development of new strategies for the diagnosis and treatment of breast cancer.
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Jerusa Araújo Quintão Arantes
authors.initials: JA
authors.lastname: Faria
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Natássia Caroline Resende
authors.initials: NC
authors.lastname: Corrêa
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: de Andrade
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: de Angelis Campos
authors.affiliation: Laboratory of Molecular Pathology of cancer, Faculty of Health Sciences, University of Brasília (UnB), Brasília, DF, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Dos Santos Samuel de Almeida
authors.affiliation: Computer department, Federal Center of Technological Education of Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Thiago Souza
authors.initials: TS
authors.lastname: Rodrigues
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Alfredo Miranda
authors.initials: AM
authors.lastname: de Goes
authors.affiliation: Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: Laboratory of Molecular Pathology of cancer, Faculty of Health Sciences, University of Brasília (UnB), Brasília, DF, Brazil.
authors.forename: Fábio Pittella
authors.initials: FP
authors.lastname: Silva
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