Abstract:
:Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Crujeiras AB,Diaz-Lagares A,Stefansson OA,Macias-Gonzalez M,Sandoval J,Cueva J,Lopez-Lopez R,Moran S,Jonasson JG,Tryggvadottir L,Olafsdottir E,Tinahones FJ,Carreira MC,Casanueva FF,Esteller Mdoi
10.1530/ERC-16-0565subject
Has Abstractpub_date
2017-07-01 00:00:00pages
351-363issue
7eissn
1351-0088issn
1479-6821pii
ERC-16-0565journal_volume
24pub_type
杂志文章abstract::Autotaxin is a secreted enzyme that converts extracellular lysophosphatidylcholine to lysophosphatidate (LPA). In cancers, LPA increases tumour growth, metastasis and chemoresistance by activating six G-protein coupled receptors. We examined >200 human thyroid biopsies. Autotaxin expression in metastatic deposits and ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-15-0045
更新日期:2015-08-01 00:00:00
abstract::The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key signaling pathway that has been linked to both tumorigenesis and resistance to therapy in prostate cancer and other solid tumors. Given the significance of the PI3K/Akt/mTOR pathway in integrating cell survival signals a...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-12-0394
更新日期:2013-05-20 00:00:00
abstract::Epidemiologic and experimental evidence suggest that a subset of breast cancer is insulin responsive, but it is unclear whether safe and effective therapies that target the insulin receptor (IR), which is homologous to oncogenes of the tyrosine kinase class, can be developed. We demonstrate that both pharmacologic inh...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0136
更新日期:2011-11-14 00:00:00
abstract::The potential of aromatase (estrogen synthetase) within the breast to provide a significant source of estrogen mediating tumor proliferation is suggested by studies reporting 4- to 6-fold higher estrogen levels in tumors than in plasma of postmenopausal patients with breast cancer. Recent studies in our laboratory hav...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0060205
更新日期:1999-06-01 00:00:00
abstract::Malignant growth of small-cell lung carcinoma is promoted by various neuroendocrine autocrine/paracrine loops. Therefore, to interfere with this mitogenic process, it is crucial to elucidate the mechanisms involved. It is known that the oxytocin (OT) and vasopressin (VP) genes, normally transcriptionally restricted in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00803
更新日期:2004-12-01 00:00:00
abstract::The study aims to examine whether the annual variations in fasting plasma glucose (FPG) measurements, represented by the coefficient of variation (CV), predict cancer incidence and mortality in the subsequent years independent of traditional risk factors of type 2 diabetic patients. A computerized database of patients...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-12-0038
更新日期:2012-07-18 00:00:00
abstract::The HIV protease inhibitor Nelfinavir (NFV) inhibits PI3K/AKT and MAPK/ERK signaling pathways, emerging targets in thyroid cancers. We examined the effects of NFV on cancer cells that derived from follicular (FTC), papillary (PTC) and anaplastic (ATC) thyroid cancers. NFV (1-20 µM) was tested in FTC133, BCPAP and SW17...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0568
更新日期:2017-03-01 00:00:00
abstract::The concentrations of endogenous hormones differ between women with twin and singleton births, with a possible influence on the risk of cancer. We used the nationwide Swedish Family-Cancer Database, including 30,409 women with a twin birth, to examine the subsequent risks of breast, endometrial, and ovarian cancers. R...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0088
更新日期:2007-09-01 00:00:00
abstract::The clinical course of medullary thyroid carcinoma (MTC) associated with the MEN2A syndrome as well as of sporadic MTC shows considerable heterogeneity. The disease picture varies not only between the same RET proto-oncogene mutation carriers but also among sporadic MTC patients with no RET germinal mutations, which s...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-17-0452
更新日期:2018-04-01 00:00:00
abstract::Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We ther...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-17-0445
更新日期:2018-03-01 00:00:00
abstract::Distant metastases from thyroid cancer of follicular origin are uncommon. Treatment includes levothyroxine administration, focal treatment modalities with surgery, external radiation therapy and thermal ablation, and radioiodine in patients with uptake of 131I in their metastases. Two-thirds of distant metastases beco...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0542
更新日期:2018-04-01 00:00:00
abstract::Dendritic cells (DCs) are highly efficient antigen-presenting cells in the immune system with the potential to regulate the system and induce a cytotoxic T-cell response. As a proof of principle, a multitude of animal and human studies has demonstrated that immunization with antigen-loaded DCs may lead to anti-tumour ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.01133
更新日期:2006-09-01 00:00:00
abstract::In the CLARINET study, lanreotide Autogel (depot in USA) significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal neuroendocrine tumours (NETs). We report long-term safety and additional efficacy data from the open-label extension (OLE). Patients with metastatic grade 1...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1530/ERC-15-0490
更新日期:2016-03-01 00:00:00
abstract::Neuroendocrine tumours (NET) of the gastroenteropancreatic system comprise a malignant entity with a low incidence. Only limited information is available on long-term clinical outcome and clinically applicable prognostic factors. We performed a retrospective analysis of a large, well-characterized centre-based patient...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0017
更新日期:2008-12-01 00:00:00
abstract::We undertook this study to estimate an accurate incidence and spread patterns of occult papillary thyroid carcinoma (PTC) in patients with a preoperative diagnosis of solitary PTC by using whole-specimen mapping of all specimens after a total thyroidectomy. Enrolled prospectively in this whole-thyroid mapping study ar...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-15-0152
更新日期:2015-08-01 00:00:00
abstract::With increasing numbers of childhood cancer survivors who were treated with radiation, there is a need to evaluate potential biomarkers that could signal an increased risk of developing thyroid cancer. We aimed to examine the relationships between thyrotropin and thyroglobulin levels and the risk of developing thyroid...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-17-0408
更新日期:2018-04-01 00:00:00
abstract::Metastatic tumor cells can interfere directly with the function of bone cells involved in normal bone remodeling or indirectly by influencing the behavior of hematopoietic, stromal and other cells in bone marrow that interact with bone cells. Recent studies of metastatic cancer have revealed that tumor cells interact ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0060333
更新日期:1999-09-01 00:00:00
abstract::The androgen receptor (AR) is well known to play a central role in the pathogenesis of prostate cancer (PCa). In several studies, AR was overexpressed in castration-resistant PCa (CRPC). However, the mechanism of AR overexpression in CRPC is not fully elucidated. Y-box binding protein-1 (YB-1) is a pleiotropic transcr...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0017
更新日期:2011-07-11 00:00:00
abstract::Thirty percent of medullary thyroid carcinomas (MTCs) are related to dominant germline pathogenic variants in the RET proto-oncogene. According to their aggressiveness, these pathogenic variants are classified in three risk levels: 'moderate', 'high' and 'highest'. The present study compares the metabolomics profiles ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0314
更新日期:2019-03-01 00:00:00
abstract::Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved in DIO3 upregulation in PTC. Experiments were performed in...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-15-0162
更新日期:2016-03-01 00:00:00
abstract::The leucine-rich repeats and immunoglobulin-like domains (LRIG) family of transmembrane proteins contains three vertebrate members (LRIG1, LRIG2 and LRIG3) and one member each in flies (Lambik) and worms (Sma-10). LRIGs have stepped into the spotlight as essential regulators of growth factor receptors, including recep...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0179
更新日期:2014-01-01 00:00:00
abstract::The fight against cancer has seen major breakthroughs in recent years. More than a decade ago, tyrosine kinase inhibitors targeting constitutively activated signaling cascades within the tumor inaugurated a new era of oncological therapy. Recently, immunotherapy with immune checkpoint inhibitors has started to revolut...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0169
更新日期:2016-10-01 00:00:00
abstract::Prostate cancer (PCa) is one of the most common causes of male cancer-related death in Western nations. The cellular response to androgens is mediated via the androgen receptor (AR), a ligand-inducible transcription factor whose dysregulation plays a key role during PCa development and progression following androgen d...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-12-0401
更新日期:2013-03-26 00:00:00
abstract::Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cau...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0580
更新日期:2015-06-01 00:00:00
abstract::Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour suppressor. To investigate the in vivo role of menin, we developed a mouse model, by dele...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0082
更新日期:2009-12-01 00:00:00
abstract::We report the case of an 8-year-old child who presented with severe hyperinsulinaemic hypoglycaemia due to a pancreatic islet cell adenoma. In vivo, there was no beneficial response to the hyperglycaemia-inducing agent diazoxide and as a consequence the child underwent a subtotal pancreatectomy. In vitro studies of ad...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.0.0090221
更新日期:2002-12-01 00:00:00
abstract::It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0092
更新日期:2008-03-01 00:00:00
abstract::Pituitary tumor-transforming gene 1-binding factor (PTTG1IP; PBF) is a multifunctional glycoprotein, which is overexpressed in a wide range of tumours, and significantly associated with poorer oncological outcomes, such as early tumour recurrence, distant metastasis, extramural vascular invasion and decreased disease-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0340
更新日期:2017-09-01 00:00:00
abstract::The androgen receptor (AR) mediates the effects of male steroid hormones (androgens) and contributes to a wide variety of physiological and pathophysiological conditions. As such, the regulatory mechanisms governing AR activity are of high significance. Concerted effort has been placed on delineating the mechanisms th...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.01115
更新日期:2006-12-01 00:00:00
abstract::Somatostatin-producing neuroendocrine tumors (SOM-NETs) of the duodenum and pancreas appear to be heterogeneous. To determine their clinicopathological profiles, respective data were analyzed on a series of 82 duodenal and 541 pancreatic NETs. In addition, the clinical records of 821 patients with duodenal or pancreat...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究
doi:10.1677/ERC-07-0157
更新日期:2008-03-01 00:00:00