title: N-myc downstream-regulated gene 1 (NDRG1) a differentiation marker of human breast cancer.
abstract: N-myc downstream-regulated gene 1 (NDRG1), also called differentiation-related gene-1 (Drg1) and Cap43, is expressed in various normal tissues and suppressed in several malignancies. In this study, whether NDRG1 expression was correlated with differentiation of human breast cancer cells has been investigated. Endogenous expression level of NDRG1 was closely correlated with differentiation status of breast cancer cell lines. Furthermore, sodium butyrate (NaB), an inducer of cellular differentiation, increased the expression of β-casein, a milk-related differentiation marker, together with up-regulation of NDRG1 in breast cancer cells. In contrast, inhibition of NDRG1 by its siRNA resulted in reduced accumulation of β-casein. Immunohistochemical analysis showed co-expression of NDRG1 and β-casein or milk fat protein (MFP), another differentiation marker of breast tissue, in the mouse xenograft model of breast cancer. Furthermore, overexpression of NDRG1 expanded the differentiated area in the xenograft model of breast cancer. In human breast cancer, using samples from 45 patients, we also showed close relationship between NDRG1 and β-casein or MFP expression. Altogether, in vitro and in vivo data demonstrated a possible role of NDRG1 in differentiation of breast cancer. We concluded that NDRG1 could be used as a biomarker for differentiation of breast cancer for both diagnostic and therapeutic purposes.
authors.affiliation: Institute of Cancer Innovative Therapy, Kurume University, Kurume, Japan. fotovati@kyudai.jp
authors.forename: Abbas
authors.initials: A
authors.lastname: Fotovati
authors.forename: Samah
authors.initials: S
authors.lastname: Abu-Ali
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamana
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002364:Caseins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011379:Prognosis; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D002364:Caseins; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D000099259:N-myc Downstream-Regulated Gene 1 Protein