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 their expression, are activated in small-cell lung cancer (SCLC), concomitantly with expression of their receptors (OTR, V1aR, V1bR/V3R and V2R). The aim of the present study was to characterize, in concentrations close to physiological and pharmacological conditions, intracellular signalling events triggered by OT and VP binding to their specific receptors in SCLC cells and to identify factors mediating OT- and VP-induced mitogenic effects on SCLC. Known agonists for OTR ([Thr4,Gly7]OT) and V1aR (F180), in addition to OT and VP, were able to elicit increases in cytosolic Ca2+ levels and this effect could be blocked using an OTR antagonist (OVTA) or a V1aR antagonist (SR49059) respectively. There was no activation of the cAMP pathway detected after VP, dDAVP (a V2R agonist), or OT treatment. Stimulation of SCLC cells with OT and VP led to an increase of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, maximal at 5 min, and the subsequent phosphorylation of its downstream target p90 ribosomal S6 kinase (p90RSK). Pre-incubation with OVTA and SR49059, and with inhibitors of phospholipase C (PLC), protein kinase C (PKC), mitogen-activated protein kinase/ERK kinase (MEK) 1/2 and a Ca2+ chelator significantly reduced OT- and VP-induced ERK1/2 phosphorylations. OVTA, SR49059 as well as MEK1/2 and PKC inhibitors also downregulated OT- and VP-induced p90RSK phosphorylation. In [3H]thymidine-uptake experiments, we subsequently observed that PLC, Ca2+, PKC and ERK1/2 are absolutely required for the OT- and VP-stimulated SCLC cellular growth process. In conclusion, the results presented here indicate that OT- and VP-induced mitogenic effects on SCLC are respectively mediated by OTR and V1aR signalling and that this mitogenic signalling passes through the phosphorylation of ERK1/2 and p90RSK in a PLC-, Ca2+-, PKC- and MEK1/2-dependent pathway.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Péqueux C,Keegan BP,Hagelstein MT,Geenen V,Legros JJ,North WGdoi
10.1677/erc.1.00803subject
Has Abstractpub_date
2004-12-01 00:00:00pages
871-85issue
4eissn
1351-0088issn
1479-6821pii
11/4/871journal_volume
11pub_type
杂志文章abstract::This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused by a solid fibrous ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/ERC-07-0161
更新日期:2007-12-01 00:00:00
abstract::Oestrogen receptors (ESRs) regulate the growth and differentiation of normal ovarian epithelia. However, to date their role as biomarkers in the clinical setting of ovarian cancer remains unclear. In view of potential endocrine treatment options, we tested the role of ESR1 mRNA expression in ovarian cancer in the cont...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0342
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abstract::Deprivation of estrogen causes breast tumors in women to adapt and develop enhanced sensitivity to this steroid. Accordingly, women relapsing after treatment with oophorectomy, which substantially lowers estradiol for a prolonged period, respond secondarily to aromatase inhibitors with tumor regression. We have utiliz...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01018
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-19-0434
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-13-0132
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abstract::Transformation-related protein 63 (Trp63), the predominant member of the Trp53 family, contributes to epithelial differentiation and is expressed in breast neoplasia. Trp63 features two distinct promoters yielding specific mRNAs encoding two major TRP63 isoforms, a transactivating transcription factor and a dominant n...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0032
更新日期:2014-05-06 00:00:00
abstract::PD-L1 expression is being considered a potential biomarker for response of anti-PD-1 or anti-PD-L1 agents in various tumors. The reported frequency of PD-L1 positivity varies in thyroid carcinomas, and multiple factors may contribute to the variability in PD-L1 positivity. We evaluated the PD-L1 expression in various ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0421
更新日期:2017-02-01 00:00:00
abstract::Androgen deprivation therapy (ADT) is a highly effective treatment used in ∼30% of men with prostate cancer. Adverse effects of ADT on muscle are significant with consistent losses in muscle mass. However, effects of ADT on muscle strength and physical function, of most relevance to the patient, are less well understo...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0232
更新日期:2016-01-01 00:00:00
abstract::Mouse models of prostate cancer (PCa) are critical for understanding the biology of PCa initiation, progression, and treatment modalities. Here, we summarize recent advances in PCa mouse models that led to new insights into specific gene functions in PCa. For example, the study of transgenic mice with TMPRSS2/ERG, an ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-12-0285
更新日期:2013-06-24 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:2015-06-01 00:00:00
abstract::Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of <10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging ...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/ERC-07-0045
更新日期:2007-09-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-09-0008
更新日期:2009-06-01 00:00:00
abstract::Forty years ago, physicians caring for the J-kindred, a 100+ member family with multiple endocrine neoplasia type 2A (MEN2A), hypothesized that early thyroidectomy based on measurement of the biomarker calcitonin could cure patients at risk for development of medullary thyroid carcinoma (MTC). We re-evaluated 22 famil...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-20-0108
更新日期:2020-08-01 00:00:00
abstract::Overexpression of human epidermal growth factor receptor 2 (HER2) predicts response to anti-HER2 therapy in breast cancer. We investigated whether hormone receptor (HR) status influences the treatment benefit of trastuzumab in patients with breast cancer. Data from 8338 patients with primary nonmetastatic breast cance...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0084
更新日期:2016-05-01 00:00:00
abstract::Aromatase inhibitors (AIs) are one of the principal therapeutic approaches for estrogen receptor-positive (ER+) breast cancer in postmenopausal women. They block estrogen biosynthesis through aromatase inhibition, thus preventing tumour progression. Besides the therapeutic success of the third-generation AIs, acquired...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0425
更新日期:2018-05-01 00:00:00
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-10-0148
更新日期:2010-12-21 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-08-0002
更新日期:2008-06-01 00:00:00
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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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
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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更新日期:2008-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1677/erc.1.00936
更新日期:2005-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-15-0461
更新日期:2016-02-01 00:00:00
abstract::Medullary thyroid cancer (MTC) is a rare tumor arising from the calcitonin-producing parafollicular C cells of the thyroid gland, occurring either sporadically or alternatively in a hereditary form based on germline RET mutations in approximately one-third of cases. Historically, patients with advanced, metastasized M...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0104
更新日期:2016-06-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.01239
更新日期:2006-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-17-0196
更新日期:2017-08-01 00:00:00
abstract::Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a heat shock protein 90 (HSP90) molecular chaperone upregulated in several human malignancies and involved in protection from apoptosis and drug resistance, cell cycle progression, cell metabolism and quality control of specific client proteins. TRAP1 role...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
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更新日期:2016-09-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1677/ERC-09-0104
更新日期:2009-12-01 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
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更新日期:2018-03-01 00:00:00