title: Epigenetic silencing of HOPX contributes to cancer aggressiveness in breast cancer.
abstract: Epigenetic silencing of HOPX has been shown to be frequent and specific in human cancers. HOPX is thought as a tumor suppressor gene and its promoter methylation is the main mechanism of down-regulation. In non-hereditary breast cancer, since roles of epigenetic modifications are more critical than in other cancers, the aim of this study is to seek into the roles and clinical relevance of epigenetic silencing of HOPX. Down-regulation of HOPX was observed in all human breast cancer cell lines tested. The promoter methylation was found in six of seven cell lines, and demethylating agents restored HOPX expression. The promoter methylation was cancer-specific in human breast tissues. Forced expression of HOPX attenuated anchorage-independent growth in vitro. HOPX promoter methylation independently predicted worse prognosis of breast cancer patients. Of note, HOPX promoter methylation was significantly associated with HER2 positivity as well as advanced lymph node metastasis. HOPX promoter methylation is not only frequent and cancer-specific but also associated with aggressive phenotype in breast cancer. Epigenetic silencing of HOPX may have clinical potential as a biomarker in the treatment strategy of breast cancer patients.
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katoh
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Waraya
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishii
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nishizawa
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Minatani
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ema
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kosaka
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tanino
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Surgery, Kitasato University School of Medicine, Kanagawa, Japan. Electronic address: intl-aff@kitasato-u.ac.jp.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D009361:Neoplasm Invasiveness; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C476884:HOPX protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Epigenetic silencing; HER2; HOPX