The oviduct produces erythropoietin in an estrogen- and oxygen-dependent manner

Masuda, Seiji; Kobayashi, Toshihiro; Chikuma, Mariko; Nagao, Masaya; Sasaki, Ryuzo

doi:10.1152/ajpendo.2000.278.6.e1038

Cited by 86 publications

(49 citation statements)

References 45 publications

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“…Our data suggest that factors other than hypoxia in tumor cells may contribute to EPO expression in breast cancer cells. Transcriptional up-regulation of EPO mRNA expression in an estrogen-dependent manner in the female reproductive tract in the uterus (Yasuda et al, 1998) and oviduct (Masuda et al, 2000) suggests that estrogen may play a role in EPO expression in breast cancer cells. Our sample size was too small to establish a meaningful correlation between estrogen receptor status and EPO expression in the tumor specimens, and further analysis of a larger series will be required.…”

Section: Discussionmentioning

confidence: 99%

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Functional Significance of Erythropoietin Receptor Expression in Breast Cancer

Arcasoy

Amin

Karayal

et al. 2002

Laboratory Investigation

165

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SUMMARY: Erythropoietin (EPO) is the principal hematopoietic cytokine that regulates mammalian erythropoiesis by binding to its transmembrane receptor EpoR. Recent experimental evidence suggests that the biologic effects of EPO are not limited to the regulation of erythropoiesis. In studies focusing on nonhematopoietic effects of EpoR signaling, we found high levels of EpoR protein expression in human breast cancer cells. The purpose of the present study was to evaluate clinical breast cancer specimens for EPO and EpoR expression, characterize the relationship between EPO expression and tumor hypoxia in biopsies prelabeled with hypoxia marker pimonidazole, analyze breast cancer cell lines for EpoR expression, and study the functional significance of EpoR expression in breast cancer cells in vivo. Immunohistochemical analysis for EPO, EpoR expression, and pimonidazole adducts was performed on 26 tumor biopsies with contiguous sections from 10 patients with breast cancer. High levels of EpoR expression were found in cancer cells in 90% of tumors. EPO expression was found in 60% of tumors and EPO and EpoR colocalization in tumor cells was present in many cases. The expression pattern of EPO with respect to tumor hypoxia was variable, without consistent colocalization of EPO and hypoxia in tumor cells. Human and rat breast cancer tissue culture cells express EpoR mRNA and protein. To study the in vivo function of EpoR expression in breast cancer cells, we used rat syngeneic R3230Ac mammary adenocarcinoma cells in a tumor Z-chamber model (dual porous plexiglass chambers containing fibrin gel, cancer cells, and a putative anti-tumor compound implanted into the subcutaneous tissue of rats). Local, one-time administration of a neutralizing anti-EPO antibody, soluble EPO receptor, or an inhibitor of Jak2, a cytoplasmic tyrosine kinase essential for EPO-mediated mitogenesis, resulted in a delay in tumor growth with 45% reduction in maximal tumor depth in tumor Z-chambers in a dose-dependent manner. These studies demonstrate the expression of functional receptors for EPO in breast cancer cells. (Lab Invest 2002, 82:911-918).

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Section: Discussionmentioning

confidence: 99%

“…More recently, estrogen-dependent EPO production was demonstrated in the female reproductive tract, specifically in the uterus (Yasuda et al, 1998) and oviduct (Masuda et al, 2000). Another study reported EPO expression in lactating breast (Juul et al, 2000).…”

mentioning

confidence: 98%

Functional Significance of Erythropoietin Receptor Expression in Breast Cancer

Arcasoy

Amin

Karayal

et al. 2002

Laboratory Investigation

165

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“…In an earlier study the elevation of liver Epo production after bile duct ligation has been shown [98] . Data on the possibility of tissue specific estrogen modulation of local Epo expression together with elevation of estrogen receptor expression in human cholangiocarcinoma are also of great interest in this connection [6,86,99,100] .…”

Section: Alterations Of Local and Systemic Hgf Levelmentioning

confidence: 99%

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

Smirnova¹

2007

WJG

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The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes, cholangiocarcinoma predisposition and development. Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

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“…14). Indeed, in female reproductive organs, EPO/EPOR expression is regulated by estrogen and/or progesterone (15)(16)(17)(18)(19)(20). Nevertheless, no conclusive data exist on the correlation of EPO/EPOR with steroid receptors in normal mammary gland and breast carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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

Pelekanou

Kampa

Kafousi³

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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)

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The oviduct produces erythropoietin in an estrogen- and oxygen-dependent manner

Cited by 86 publications

References 45 publications

Functional Significance of Erythropoietin Receptor Expression in Breast Cancer

Functional Significance of Erythropoietin Receptor Expression in Breast Cancer

JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

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

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