Erythropoietin and Its Receptor in Breast Cancer: Correlation with Steroid Receptors and Outcome

Abstract

Autocrine/paracrine erythropoietin (EPO) action, promoting cell survival and mediated by its receptor (EPOR) in various solid tumors, including breast carcinoma, questions about the prognostic and therapeutic interest of this system. The expression of EPO/EPOR is steroid dependent in some tissues; however, a clear relationship of EPO/EPOR and steroid receptors in breast cancer has not been established thus far. Recently, the field of steroid receptors has expanded, including rapid effects mediated by membrane-associated receptors, regulating cell survival or apoptosis. The aim of this study was to evaluate EPO/EPOR and membrane-associated steroid receptor expression in breast carcinoma, in view of their prognostic significance, compared with other established markers [estrogen receptor (ER)-progesterone receptor (PR) status and Her2 expression] and hypoxia-induced factor 1 nuclear localization in 61 breast cancer specimens followed for V90 months. We report that EPO-EPOR were expressed in 80% and 84% of samples, although 8% and 2% of nontumoral fields expressed EPO/EPOR too. Membrane-associated receptors for estrogen (mER), progesterone (mPR), and androgen (mAR) were expressed in 96%, 94%, and 93% of cases. Significant correlations between EPO-hypoxiainduced factor 1A, mER-ER, mER-EPO, mAR-EPOR, and mER-mPR-Her2 were found. Finally, EPO, EPOR, and mAR are inversely related to disease-free and overall survival. However, in view of the above correlations, we conclude that EPO/EPOR and membrane steroid receptors are not independent prognostic markers as they are closely related to other established markers. In contrast, they may represent possible new therapeutic targets. (Cancer Epidemiol Biomarkers Prev 2007; 16(10):2016-23)

Expression of Hypoxia-Inducible Factor 1α in Invasive Breast Cancer with Metastasis to Lymph Nodes: Correlation with Steroid Receptors, HER2 and EPO-R

“…In our study, we found EPO-R expression in 36.2% of cases, and Pelekanou et al showed that in 50 cases (82%) the tumor mass was positive for EPO-R, with staining being more intense at the growing edge of the tumor [31]. In our material we also evaluated the relationship between clinical features, such as histological grade of malignancy, tumor size or presence of lymph node metastases and expression of HIF-1α, and receptor for EPO, but no statistically significant correlations were demonstrated.…”

Erythropoietin-Induced Activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK Pathways Promotes Malignant Cell Behavior in a Modified Breast Cancer Cell Line

“…36). An inverse relationship between EpoR expression and disease-free and overall survival in breast cancer has been reported (37) and Epo may only have a negative effect in cancers that are positive for EpoR expression using immunohistochemistry (35). However, further studies are needed with more specific antibodies and greater sample numbers to determine the prognostic significance of EpoR expression on tumors.…”

Novel Oligomeric Proanthocyanidin Derivatives Interact with Membrane Androgen Sites and Induce Regression of Hormone-Independent Prostate Cancer

“…Membrane androgen binding sites have been reported in a number of normal or malignant tissues and lesions. In particular, androgen sites have been detected in T lymphocytes (Benten et al, 1999), spermocytes and sperm (Walker, 2003), breast cancer (Pelekanou et al, 2007), prostate cancer , and colon cancer (Gu et al, 2009). In both breast and prostate, membrane-acting androgen have been reported to induce tumor regression alone (Hatzoglou et al, 2005) or in combination with cytoskeletal acting drugs (Kampa et al, 2006), suggesting a potential therapeutic role of membrane androgen agonists in breast and prostate cancer.…”