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)alpha-positive tissues in mice. Human 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 carcinogenisis. Given that ER is over-expressed in a large proportion of breast cancers, we reasoned that EFP may play a role in mediating the estrogen-dependent 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 medium, suggesting that it may be secreted. Immunohistochemistry of paraffin-embedded breast biopsy specimens showed significantly greater levels of EFP in lactating breast and fibroadenomata compared to normal breast (p<0.001 and p = 0.001, respectively), which is likely to be a result of estrogen responsiveness. Levels were reduced in breast cancer (p = 0.02), where no correlation was seen with other immunohistochemical, histopathological or clinical data. The lack of correlation between EFP and ER status of tumors could indicate escape from estrogenic control, pointing to new models of tumor pathogenesis. Increased levels of EFP in lactating breast and the reduction in malignancy suggest a role for EFP in promoting mammary gland differentiation.
Thomson
S D
SD
CRC Laboratories, Department of Cancer Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, UK.
Ali
S
S
Pickles
L
L
Taylor
J
J
Pace
P E
PE
Lymboura
M
M
Shousha
S
S
Coombes
R C
RC
D000818:Animals; D001706:Biopsy; D001940:Breast / Q000737:chemistry*; D001943:Breast Neoplasms / Q000737:chemistry*; D019556:COS Cells; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis* / Q000737:chemistry*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D016335:Zinc Fingers
D003470:Culture Media; D004268:DNA-Binding Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases