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Reduced expression of oestrogen receptor β in invasive breast cancer and its re‐expression using DNA methyl transferase inhibitors in a cell line model
Author(s) -
Skliris George P,
Munot Kailas,
Bell Sandra M,
Carder Pauline J,
Lane Sally,
Horgan Kieran,
Lansdown Mark RJ,
Parkes Alicia T,
Hanby Andrew M,
Markham Alexander F,
Speirs Valerie
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1436
Subject(s) - cancer research , breast cancer , carcinogenesis , immunohistochemistry , dna methylation , estrogen receptor , tamoxifen , lymph node , cancer , biology , gene silencing , pathology , medicine , gene expression , gene , biochemistry
To gain insights into the possible role of oestrogen receptor (ER) β in breast carcinogenesis, immunohistochemical analysis of ER β was performed on 512 breast specimens encompassing normal ( n = 138), pure ductal carcinoma in situ ( n = 16), invasive cancers ( n = 319), lymph node metastases ( n = 31), and recurrences ( n = 8). Real‐time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER β gene in the ER β negative breast cancer cell lines SkBr3 and MDA‐MB‐435. A gradual reduction in, but not a complete loss of, ER β expression was observed during the transition from normal and pre‐invasive lesions to invasive cancers, where ER β was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER β‐positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER β was present in the primary tumour, it persisted in the metastasis. Treatment of ER β‐negative cell lines with DNA methyl transferase inhibitors restored ER β expression, providing experimental evidence that silencing of ER β in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER β expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation. Copyright © 2003 John Wiley & Sons, Ltd.