Abstract:
:Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERalpha and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competitive anti-oestrogen tamoxifen (TAM) on oestrogen and IGF signalling in these cells. Wt MCF-7 and LTED cells were treated with a log 7 concentration range of E2, TAM or ICI. Effects on cell growth, ERalpha transactivation, expression of ERalpha, ERbeta and components of the IGF pathway were measured with and without insulin. In the presence of insulin, growth of LTED cells was refractory to TAM but inhibited by ICI and E2. In the absence of insulin, LTED cells showed persistent hypersensitivity to E2, and remained inhibited by ICI but were largely unaffected by TAM. ICI but not TAM inhibited ER-mediated gene transcription and treatment with ICI resulted in a dose-dependent reduction in ERalpha levels whilst having no effect on ERbeta expression. IGF-I receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF-7 cells, and ICI but not TAM reduced their expression in a dose-dependent fashion. Thus IGF signalling as well as ERalpha expression and function are enhanced during LTED. While the resultant cells are resistant to TAM, ICI down-regulates ERalpha, reducing IGF signalling and cell growth. These results support the use of ICI in women with ER-positive breast cancer who have relapsed on an aromatase inhibitor.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Martin LA,Pancholi S,Chan CM,Farmer I,Kimberley C,Dowsett M,Johnston SRdoi
10.1677/erc.1.00905subject
Has Abstractpub_date
2005-12-01 00:00:00pages
1017-36issue
4eissn
1351-0088issn
1479-6821pii
12/4/1017journal_volume
12pub_type
杂志文章abstract::Ghrelin is a hormone with multiple physiologic functions, including promotion of growth hormone release, stimulation of appetite and regulation of energy homeostasis. Treatment with ghrelin/ghrelin-receptor agonists is a prospective therapy for disease-related cachexia and malnutrition. In vitro studies have shown hig...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0130
更新日期:2016-09-01 00:00:00
abstract::Na(+)/I(-) symporter (NIS)-mediated radioiodide uptake (RAIU) serves as the basis for targeted ablation of thyroid cancer remnants. However, many patients with thyroid cancer have reduced NIS expression/function and hence do not benefit from radioiodine therapy. microRNA (miR) has emerged as a promising therapeutic ta...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0439
更新日期:2015-02-01 00:00:00
abstract::The 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) held in Houston, TX, USA, focused on emerging topics in the pathogenesis and therapy of malignant endocrine tumors associated with MEN syndromes. With MEN-2 syndromes, the most common malignancy is medullary thyroid carcinoma (MTC). In the spirit o...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-20-0110
更新日期:2020-08-01 00:00:00
abstract::Although targeted therapy, including inhibitors of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor, being developed for carcinoids arised from the gastrointestinal tract, treatment for locally advanced or metastatic bronchial carcinoids (BCs) remains lacking. Traditional cytotoxic chemother...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0290
更新日期:2011-04-28 00:00:00
abstract::Pheochromocytomas are catecholamine-producing tumors which are generally benign, but which can also present as or develop into malignancy. Molecular pathways of malignant transformation remain poorly understood. Pheochromocytomas express various trophic peptides which may influence tumoral cell behavior. Here, we inve...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-10-0109
更新日期:2010-06-25 00:00:00
abstract::Although the authors of the present review have contributed to genetic discoveries in the field of pheochromocytoma research, we can legitimately ask whether these advances have led to improvements in the diagnosis and management of patients with pheochromocytoma. The answer to this question is an emphatic Yes! In the...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-18-0085
更新日期:2018-08-01 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::Selection of novel molecular markers is an important goal of cancer genomics studies. The aim of our analysis was to apply the multivariate bioinformatical tools to rank the genes - potential markers of papillary thyroid cancer (PTC) according to their diagnostic usefulness. We also assessed the accuracy of benign/mal...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-06-0048
更新日期:2007-09-01 00:00:00
abstract::The cancer stem cell model proposes that tumors have a hierarchical organization in which tumorigenic cells give rise to non-tumorigenic cells, with only a subset of stem-like cells able to propagate the tumor. In the case of prostate cancer, recent analyses of genetically engineered mouse (GEM) models have provided e...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0367
更新日期:2015-12-01 00:00:00
abstract::The destruction of proteins via the ubiquitin-proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious t...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0005
更新日期:2015-02-01 00:00:00
abstract::Pancreatic endocrine tumors (PET) represent a heterogenous group of neoplasms. Although surgical resection is considered a safe and effective treatment for many PET, therapeutic options for inoperable and progressive PET are limited. The expression of heat-shock protein (HSP) 90 was investigated in 120 clinically and ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0227
更新日期:2012-05-03 00:00:00
abstract::Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain unde...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0552
更新日期:2019-07-01 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::This review describes human and rodent-derived cell lines and xenografts developed over the last five decades that are suitable or potentially suitable models for paraganglioma-pheochromocytoma research. We outline the strengths and weaknesses of various models and emphasize the recurring theme that, despite the major...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0434
更新日期:2020-12-01 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::The treatment of hormone hypersecretory syndromes caused by neuroendocrine tumors (NETs) can be a major challenge. NETs originating from the small intestine often secrete serotonin causing flushing, diarrhea and valve fibrosis, leading to dehydration or heart failure in severe cases. NETs from the pancreas can secrete...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0538
更新日期:2017-07-01 00:00:00
abstract::The combination of pituitary adenomas (PA) and phaeochromocytomas (phaeo) or paragangliomas (PGL) is a rare event. Although these endocrine tumours may occur together by coincidence, there is mounting evidence that, in at least some cases, classical phaeo/PGL-predisposing genes may also play a role in pituitary tumori...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0241
更新日期:2015-08-01 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::Tyrosine phosphorylation plays a critical role in growth regulation, and its aberrant regulation can be involved in carcinogenesis. The association of Shc (Src homolog and collagen homolog) adaptor protein family members in tyrosine phosphorylation signaling pathway is well recognized. Shc adaptor proteins transmit ac...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/ERC-08-0179
更新日期:2009-03-01 00:00:00
abstract::Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viabili...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0329
更新日期:2016-11-01 00:00:00
abstract::'Calcitonin screening' is not accepted as the standard of care in daily practice. The clinical and surgical consequences of 'calcitonin screening' in a series of patients with mildly elevated basal calcitonin and pentagastrin stimulated calcitonin levels are presented. 260 patients with elevated basal (>10 pg/ml) and ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0059
更新日期:2009-03-01 00:00:00
abstract::Pancreatic endocrine tumours (PETs) are rare and 'indolent' neoplasms that usually develop metastatic lesions and exhibit poor response to standard medical treatments. Few studies have investigated pathways responsible for PET cell growth and invasion and no alternative therapeutic strategies have been proposed. In a ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01318
更新日期:2007-03-01 00:00:00
abstract::Androgen receptor (AR) signaling is vital to the development and function of the prostate and is a key pathway in prostate cancer. AR is differentially expressed in the stroma and epithelium, with both paracrine and autocrine control throughout the prostate. Stromal-epithelial interactions within the prostate are comm...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0138
更新日期:2014-08-01 00:00:00
abstract::The protein MENIN is the product of the multiple endocrine neoplasia type I (MEN1) gene. Altered MENIN expression is one of the few events that are clearly associated with foregut neuroendocrine tumours (NETs), classical oncogenes or tumour suppressors being not involved. One of the current challenges is to understand...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0164
更新日期:2013-10-24 00:00:00
abstract::Many clinicians prefer to avoid surgery in patients with carcinoid neoplasia, because of its slow growth and relatively favourable prognosis. Nevertheless, the commonest cause of death in patients with carcinoid is advanced metastatic disease, and both clinical and epidemiological data indicate that the more effective...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.0.0100469
更新日期:2003-12-01 00:00:00
abstract::It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =...
journal_title:Endocrine-related cancer
pub_type: 临床试验,杂志文章
doi:10.1677/erc.1.00822
更新日期:2004-12-01 00:00:00
abstract::Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not wel...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0436
更新日期:2014-06-01 00:00:00
abstract::Resistance to anoikis (matrix deprivation-induced apoptosis) is a critical component of the metastatic cascade. Molecular mechanisms underlying resistance to anoikis have not been reported in thyroid cancer cells. For an in vitro model of anoikis, we cultured follicular, papillary, and anaplastic thyroid cancer cell l...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-10-0289
更新日期:2011-09-20 00:00:00
abstract::Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0555
更新日期:2016-04-01 00:00:00
abstract::Preclinical and clinical studies support that Notch signaling may play an important oncogenic role in cancer, but there is scarce information for pituitary tumors. We therefore undertook a functional study to evaluate Notch participation in pituitary adenoma growth. Tumors generated in Nude mice by subcutaneous GH3 so...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-18-0337
更新日期:2019-01-01 00:00:00