title: Human endoplasmic reticulum oxidoreductin 1-α is a novel predictor for poor prognosis of breast cancer.
abstract: Human endoplasmic reticulum oxidoreductin 1-α (hERO1-α) is an oxidizing enzyme that exists in the endoplasmic reticulum and its expression is augmented under hypoxia. It regulates a redox state of various kinds of protein through reoxidation of "client" protein disulfide isomerase. Interestingly, although the expression of hERO1-α in normal tissues was comparatively limited, various types of cancer cells expressed it in large amounts. Therefore, we examined the role of ERO1-α in tumor growth using murine breast cancer line 4T1 and found that knockdown of murine ERO1-α inhibited in vivo tumor growth and decreased lung metastasis compared with wild-type 4T1. Moreover, we investigated the relationship between expression of hERO1-α and prognosis in breast cancer patients. Seventy-one patients with breast cancer who underwent surgery between 2005 and 2006 in Sapporo Medical University Hospital (Sapporo, Japan) were analyzed in this study. Significant differences were found between the hERO1-α-positive group (n = 33) and hERO1-α-negative group (n = 38) in nuclear grade (P < 0.001) and intrinsic subtype (P = 0.021) in univariate analysis. More importantly, in multivariate analysis of disease-free survival by Cox regression, expression of hERO1-α was the only independent prognosis factor (P = 0.035). Finally, in univariate survival analysis, patients positive for hERO1-α had significantly shorter disease-free survival and overall survival than those patients negative for hERO1-α. These findings indicate that the expression of hERO1-α in cancer cells is associated with poorer prognosis and thus can be a prognostic factor for patients with breast cancer.
authors.affiliation: Department of Surgery, Sapporo Medical University, School of Medicine, Sapporo, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kutomi
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanaka
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kajiwara
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Kukita
authors.forename: Tousei
authors.initials: T
authors.lastname: Ohmura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takamaru
authors.forename: Fukino
authors.initials: F
authors.lastname: Satomi
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010088:Oxidoreductases / Q000378:metabolism*; D011379:Prognosis
chemical_list: D008562:Membrane Glycoproteins; C405327:ERO1A protein, human; D010088:Oxidoreductases