Role of Estrogen Receptor in the Regulation of Ecto-5′-Nucleotidase and Adenosine in Breast Cancer

Abstract

Purpose:The purpose is to understand the expression of ecto-5-nucleotidase (eN), an adenosine producing enzyme with potential roles in angiogenesis, growth, and immunosuppression, in estrogen receptor (ER)-negative and -positive breast cancer.Experimental Design: We investigated the regulation of eN expression at the mRNA and protein levels by ␣ in a panel of breast cancer cell lines that differ in ER status and invasive and metastatic potential. We also determined rates of adenosine formation in cells with high and low eN expression and in ER؉ cells treated with estradiol.Results: ER-negative cells express high eN protein and mRNA levels and produce up to 104-fold more adenosine from AMP and ATP. Estradiol and antiestrogen treatments confirm that eN mRNA and protein expression and adenosine generation are negatively regulated through the ER. Endogenous expression of eN in ER؊ cells transfected with ER␣ and phorbol ester-induced eN expression in ER؉ cells

Potential prognostic biomarker CD73 regulates epidermal growth factor receptor expression in human breast cancer

“…In breast-cancer cells, CD73 expression has been shown to be regulated by estrogen receptors (ER), whereby loss of ER significantly enhances CD73 expression (17). Both tumor and host CD73 co-operatively protect tumors from incoming antitumor T cells.…”

CD73: double-breasted suit

“…However, he said there is evidence for CD73 expression in primary human tumors and that other researchers have shown a correlation between CD73 expression and lack of estrogen receptor in primary breast tumors. 3 Zijlstra said additional studies might be needed to confirm the antibody's mechanism of action in reducing primary tumor growth. He said it wasn't clear whether the anti-CD73 antibody was working by shutting off adenosine production or through antibody-dependent cellular cytotoxicity (ADCC).…”

“…He added that the team's results suggest anti-CD73 therapies might be most beneficial in patients with advanced metastatic cancer. Emma Shtivelman, director of cancer research at Bionovo Inc., noted that CD73 expression has been correlated to breast cancer cell lines that do not express estrogen receptor, 3 which is one of the three missing receptors in triple-negative breast cancers.…”

NTPDase and 5'‐nucleotidase activities in physiological and disease conditions: New perspectives for human health

“…Results demonstrated that ATP hydrolysis was enhanced and ADP hydrolysis was reduced as a function of tamoxifen use, while AMP hydrolysis was unchanged [4]. The expression of ecto-5'-nucleotidase is negatively regulated by the estrogen receptor (ER) in breast cancer cells; as ER expression decreases, ecto-5'-nucleotidase increases, leading to increased generation of adenosine, which may be related to breast cancer progression [123].…”

“…However, purinergic signaling may also have a profound impact on other more protracted reactions observed in several chronic inflammatory states, such as cell proliferation, differentiation, and apoptosis [13,20,37,123].…”