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

Abstract

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)α‐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. © 2001 Wiley‐Liss, Inc.

Estrogen-Responsive Finger Protein as a New Potential Biomarker for Breast Cancer

“…Previously, Ikeda et al (5) reported Efp mRNA expression in 9 of 15 (60.0%) breast carcinoma tissues using RNase protection assay, and Thomson et al (9) reported Efp immunoreactivity in breast carcinoma cells in 64 of 91 (70.3%) cases. The frequency and cellular localization of Efp in our present study were in good agreement with these reports (5, 9), and widespread distribution of Efp may suggest an important role of Efp in breast carcinomas.…”

“…Expression of Efp was previously reported in breast carcinoma tissues at mRNA (5) and protein levels (9). However, information on the expression of Efp in human breast carcinoma tissues is still very limited, and the biological significance of Efp remains unclear at this juncture.…”

Viral defense, carcinogenesis and ISG15: Novel roles for an old ISG

“…One recent study demonstrated that Efp levels correlated positively with ER status and lymph node status but correlated negatively with 14-3-3α levels (82). In contrast, previous studies noted no correlation between Efp and ER status in breast tumor biopsies (83) and show no significant change in Efp levels in early stages of breast carcinogenesis, despite demonstrated decrease in 14-3-3α levels (84).…”

Oestrogen causes ATBF1 protein degradation through the oestrogen-responsive E3 ubiquitin ligase EFP

“…Overexpression of EFP also makes MCF7 cells estrogen-independent, as EFP-overexpressing MCF7 cells form tumors in the absence of estrogen [19]. In human breast cancer, EFP is not only overexpressed, but its expression is positively associated with lymph node metastasis and poor prognosis of breast cancer patients [17, 20, 31]. Conversely, ATBF1 is frequently inactivated in human breast cancer and can significantly inhibit breast cancer cell growth and proliferation [7, 8, 10].…”

“…In normal breast epithelial cells, the autoregulatory feedback loop can normally run to regulate breast development since estrogen concentration, ERα status and the expression of ATBF1 and EFP are all under proper control in multiple cascades of levels [32–37]. In the initiation and progression of breast cancer, however, the autoregulatory feedback loop becomes a causal factor of breast cancer through overactivation of estrogen-ERα signaling, overexpression of EFP and inactivation of ATBF1 [6–8, 19, 20, 31, 38–40]. The overactivation of estrogen-ERα signaling, overexpression of EFP and inactivation of ATBF1 turn the autoregulatory feedback loop into a vicious circle, consequently contributing to the initiation and progression of breast cancer.…”