title: Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes.
abstract: MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin-fixed and paraffin-embedded breast cancer specimens with an anti-MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser-assisted microdissection and real-time quantitative RT-PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, β-catenin, E-cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A-like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B-like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER- breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A-like specimens, 16.4% in luminal B-like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue.
authors.affiliation: Department of Breast and Endocrine Surgery, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Iizuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Fumi
authors.initials: F
authors.lastname: Fuchinoue
authors.forename: Tetsuyo
authors.initials: T
authors.lastname: Maeda
authors.forename: Eriko
authors.initials: E
authors.lastname: Murakami
authors.forename: Yukari
authors.initials: Y
authors.lastname: Obana
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Enomoto
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tani
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sakurai
authors.forename: Sadao
authors.initials: S
authors.lastname: Amano
authors.forename: Shinobu
authors.initials: S
authors.lastname: Masuda
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics*; D016764:Cell Polarity; D005260:Female; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018396:Mucin-1; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C060192:MUC1 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; MUC1; breast cancer subtype; cell polarity; intracellular localization