title: Pattern of RECK CpG methylation as a potential marker for predicting breast cancer prognosis and drug-sensitivity.
abstract: The membrane-anchored glycoprotein RECK negatively regulates multiple metalloproteinases and is frequently downregulated in tumors. Forced RECK expression in cancer cells results in suppression of tumor angiogenesis, invasion, and metastasis in xenograft models. A previous methylome study on breast cancer tissues detected inverse correlation between RECK CpG methylation (in an intron-1 region) and relapse-free survival. In this study, we focused on another region of the RECK CpG island (a promoter/exon-1 region) and found an inverse correlation between its methylation and RECK-inducibility by an HDAC inhibitor, MS275, among a panel of breast cancer cell lines (n=15). In clinical samples (n=62), RECK intron-1 methylation was prevalent among luminal breast cancers as reported previously (26 of 38 cases; 68%) and particularly enriched in tumors of the ER+PR- subclass (10 of 10 cases) and of higher histological grades (Grade 2 and 3; 28 of 43 cases; P=0.006). In about a half of these cases, promoter/exon-1 methylation was absent, and hence, RECK may be inducible by certain drugs such as MS275. Our results indicate the value of combined use of two RECK methylation markers for predicting prognosis and drug-sensitivity of breast cancers.
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Gongping
authors.initials: G
authors.lastname: Shi
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Yuki
authors.affiliation: Department of Breast Surgery, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Department of Breast Surgery, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawata
authors.affiliation: Department of Breast Surgery, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Target Therapy and Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwaisako
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kiyotsugu
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki, 701-0192, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kurebayashi
authors.affiliation: Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|Department of Breast Surgery, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Toi
authors.affiliation: Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.|Laboratory for Malignancy Control Research, Medical Innovation Center, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects; D005091:Exons; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D061986:MCF-7 Cells; D008727:Methotrexate / Q000494:pharmacology; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D011725:Pyridines / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D058851:GPI-Linked Proteins; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C115460:RECK protein, human; C118739:entinostat; D000077209:Decitabine; D001374:Azacitidine; D008727:Methotrexate
keywords: CpG island; DNA methylation; RECK; breast cancer; entinostat