Adiponectin effects on human breast cancer cells are dependent on 17-β estradiol (original) (raw)
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Effects of adiponectin on breast cancer cell growth and signaling
British journal of cancer, 2008
Obesity is a risk factor for postmenopausal breast cancer. Adiponectin/Acrp30 is lower in obese individuals and may be negatively regulating breast cancer growth. Here we determined that five breast cancer cell lines, MDA-MB-231, MDA-MB-361, MCF-7, T47D, and SK-BR-3, expressed one or both of the Acrp30 receptors. In addition, we found that the addition of Acrp30 to MCF-7, T47D, and SK-BR-3 cell lines inhibited growth. Oestrogen receptor (ER) positive MCF-7 and T47D cells were inhibited at lower Acrp30 concentrations than ER-negative SK-BR-3 cells. Growth inhibition may be related to apoptosis since PARP cleavage was increased by Acrp30 in the ER-positive cell lines. To investigate the role of ER in the response of breast cancer cells to Acrp30, we established the MDA-ERalpha7 cell line by insertion of ER-alpha into ER-alpha-negative MDA-MB-231 cells. This line readily formed tumours in athymic mice and was responsive to oestradiol in vivo. In vitro, MDA-ERalpha7 cells were growth in...
British journal of cancer, 2008
Serum levels of adiponectin are inversely associated with breast cancer risk. In this study, its effect on growth and gene expression of MCF-7 breast cancer cells and MCF-10A human mammary epithelial cells was compared. The antiproliferative effect of adiponectin on MCF-10A cells was more pronounced and was accompanied by elevated transcript levels of caspase 1, ERbeta2, ERbeta5, TR2 and USP2. Our data suggest that upregulation of genes with known growth inhibitory or apoptotic functions in mammary epithelial cells might contribute to the protective action of this adipocytokine.
Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells
Biochemical and Biophysical Research Communications, 2006
It is well established that obesity is a risk factor for breast cancer and that blood levels of adiponectin, a hormone mainly secreted by white adipocytes, are inversely correlated with the body fat mass. As adiponectin elicits anti-proliferative effects in some cell types, we tested the hypothesis that adiponectin could influence human breast cancer MCF-7 cell growth. Here we show that MCF-7 cells express adiponectin receptors and respond to human recombinant adiponectin by reducing their growth, AMPkinase activation, and p42/p44 MAPkinase inactivation. Further, we demonstrate that the anti-proliferative effect of adiponectin involves activation of cell apoptosis and inhibition of cell cycle. These findings suggest that adiponectin could act in vivo as a paracrine/endocrine growth inhibitor towards mammary epithelial cells. Moreover, adipose adiponectin production being strongly reduced in obesity, this study may help to explain why obesity is a risk factor of developing breast cancers.
Interfering Role of ERα on Adiponectin Action in Breast Cancer
Frontiers in Endocrinology
Obesity is characterized by an excess of adipose tissue, due to adipocyte hypertrophy and hyperplasia. Adipose tissue is an endocrine organ producing many bioactive molecules, called adipokines. During obesity, dysfunctional adipocytes alter adipokine secretion, contributing to pathophysiology of obesity-associated diseases, including metabolic syndrome, type 2-diabetes, cardiovascular diseases and many types of malignancies. Circulating adiponectin levels are inversely correlated with BMI, thus adiponectin concentrations are lower in obese than normal-weight subjects. Many clinical investigations highlight that low adiponectin levels represent a serious risk factor in breast carcinogenesis, and are associated with the development of more aggressive phenotype. A large-scale meta-analysis suggests that BMI was positively associated with breast cancer mortality in women with ERα-positive disease, regardless menopausal status. This suggests the importance of estrogen signaling contribution in breast tumorigenesis of obese patients. It has been largely demonstrated that adiponectin exerts a protective role in ERα-negative cells, promoting anti-proliferative and pro-apoptotic effects, while controversial data have been reported in ERα-positive cells. Indeed, emerging data provide evidences that adiponectin in obese patients behave as growth factor in ERα-positive breast cancer cells. This addresses how ERα signaling interference may enhance the potential inhibitory threshold of adiponectin in ERα-positive cells. Thus, we may reasonably speculate that the relatively low adiponectin concentrations could be still not adequate to elicit, in ERα-positive breast cancer cells, the same inhibitory effects observed in ERα-negative cells. In the present review we will focus on the molecular mechanisms through which adiponectin affects breast cancer cell behavior in relationship to ERα expression.
Endocrine-Related Cancer, 2007
Obesity is one of the well-established risk factors for endometrial cancer. Recent clinical studies have demonstrated that circulating adiponectin concentrations are inversely correlated with the incidence of endometrial carcinoma. Such epidemiological findings are consistent with the paradoxical observations that adiponectin levels are reduced in obesity. This study investigated the direct effects of adiponectin on two endometrial carcinoma cell lines, HEC-1-A and RL95–2. These cell lines express both variants of adiponectin receptors, adipo-R1 and adipo-R2. Adiponectin treatment leads to suppression of cell proliferation in both cell types, which is primarily due to the significant increase of cell populations at G1/G0-phase and to the induction of apoptosis. The inhibition of growth in these two cell lines appears to be mediated by different signaling pathways. Although adiponectin treatment markedly increases the phosphorylation (Thr172) of AMP-activated protein kinase α in both...
Adiponectin Can Affect ER Signaling in Obese Breast Cancer Patients
2012
ABSTRACT Background: While the various antitumororal activities of adiponectin as an adipocyte-derived hormone well studied, it is speculated that there is a crosstalk between adiponectin and esterogen receptor (ER) signaling. To test this hypothesis we evaluate the possible correlation between serum level of adiponectin with two estrogen receptors (ERα and ERβ) gene expression in breast cancer patients.
The Emerging Role of Adiponectin in Female Malignancies
International Journal of Molecular Sciences
Obesity, characterized by excess body weight, is now accepted as a hazardous health condition and an oncogenic factor. In different epidemiological studies obesity has been described as a risk factor in several malignancies. Some biological mechanisms that orchestrate obesity–cancer interaction have been discovered, although others are still not completely understood. The unbalanced secretion of biomolecules, called “adipokines”, released by adipocytes strongly influences obesity-related cancer development. Among these adipokines, adiponectin exerts a critical role. Physiologically adiponectin governs glucose levels and lipid metabolism and is fundamental in the reproductive system. Low adiponectin circulating levels have been found in obese patients, in which its protective effects were lost. In this review, we summarize the epidemiological, in vivo and in vitro data in order to highlight how adiponectin may affect obesity-associated female cancers.
The Role of Adiponectin in Cancer: A Review of Current Evidence
Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents.
Multifaceted roles of Adiponectin in cancer
Best Practice & Research Clinical Endocrinology & Metabolism, 2014
Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocytesecreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy.