Analysis of estrogen-responsive finger protein expression in benign and malignant human breast

The estrogen-responsive finger protein (EFP) gene was originally identified in a screen of genomic DNA for genes containing estrogen-response elements (EREs), and its expression was subsequently shown to be estrogen regulated and correlated with estrogen receptor (ER)ar-positive tissues in mice. Hum an chromosomal mapping localized it to 17q23.1, close to BRCA1, in a region frequently lost in breast cancers. Structurally related proteins have been implicated in a variety of important cellular processes, including carcino genesis, Given that ER is over-expressed in a large proportion of breast ca ncers, we reasoned that EFP may play a role in mediating the estrogen-depen dent progression of breast cancer. We raised anti-sera to EFP and show that EFP is present in the cytoplasm in mammary cell lines and epithelial cells of normal breast tissue. Furthermore, EFP is present in cell culture mediu m, suggesting that it may be secreted. Immunohistochemistry of paraffin-emb edded breast biopsy specimens showed significantly greater levels of EFP in lactating breast and fibroadenomata compared to normal breast (p < 0.001 a nd p = 0.001, respectively), which is likely to be a result of estrogen res ponsiveness. Levels were reduced in breast cancer (p = 0.02), where no corr elation was seen with other immunohistochemical, histopathological or clini cal data The lack of correlation between EFP and ER status of tumors could indicate escape from estrogenic control, pointing to new models of tumor pa thogenesis, Increased levels of EFP in lactating breast and the reduction i n malignancy suggest a role for EFP in promoting mammary gland differentiat ion. (C) 2001 Wiley-Liss, Inc.