title: Oestrogen-induced genes in ductal carcinoma in situ: their comparison with invasive ductal carcinoma.
abstract: It is well known that oestrogens play important roles in both the pathogenesis and development of invasive ductal carcinoma (IDC) of human breast. However, molecular features of oestrogen actions have remained largely unclear in pure ductal carcinoma in situ (pDCIS), regarded as a precursor lesion of many IDCs. This is partly due to the fact that gene expression profiles of oestrogen-responsive genes have not been examined in pDCIS. Therefore, we first examined the profiles of oestrogen-induced genes in oestrogen receptor (ER)-positive pDCIS and DCIS (DCIS component (DCIS-c)) and IDC (IDC component (IDC-c)) components of IDC cases (n=4 respectively) by microarray analysis. Oestrogen-induced genes identified in this study were tentatively classified into three different groups in the hierarchical clustering analysis, and 33% of the genes were predominantly expressed in pDCIS rather than DCIS-c or IDC-c cases. Among these genes, the status of MYB (C-MYB), RBBP7 (RBAP46) and BIRC5 (survivin) expressions in carcinoma cells was significantly higher in ER-positive pDCIS (n=53) than that in ER-positive DCIS-c (n=27) or IDC-c (n=27) by subsequent immunohistochemical analysis of the corresponding genes (P<0.0001, P=0.03 and P=0.0003 respectively). In particular, the status of C-MYB immunoreactivity was inversely (P=0.006) correlated with Ki67 in the pDCIS cases. These results suggest that expression profiles of oestrogen-induced genes in pDCIS may be different from those in IDC; and C-MYB, RBAP46 and survivin may play important roles particularly among oestrogen-induced genes in ER-positive pDCIS.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aobaku, Sendai, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ebata
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Onodera
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ishida
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamaki
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000187:drug effects; D006801:Humans; D046228:Microarray Analysis; D008875:Middle Aged; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D004967:Estrogens