Abstract:
:Pancreatic neuroendocrine neoplasms (PNENs) constitute a rare tumour entity, and prognosis and treatment options depend on tumour-mediating hallmarks such as angiogenesis, proliferation rate and resistance to apoptosis. The molecular pathways that determine the malignant phenotype are still insufficiently understood and this has limited the use of effective combination therapies in the past. In this study, we aimed to characterise the effect of the oncogenic transcription factor Cut homeobox 1 (CUX1) on proliferation, resistance to apoptosis and angiogenesis in murine and human PNENs. The expression and function of CUX1 were analysed using knockdown and overexpression strategies in Ins-1 and Bon-1 cells, xenograft models and a genetically engineered mouse model of insulinoma (RIP1Tag2). Regulation of angiogenesis was assessed using RNA profiling and functional tube-formation assays in HMEC-1 cells. Finally, CUX1 expression was assessed in a tissue microarray of 59 human insulinomas and correlated with clinicopathological data. CUX1 expression was upregulated during tumour progression in a time- and stage-dependent manner in the RIP1Tag2 model, and associated with pro-invasive and metastatic features of human insulinomas. Endogenous and recombinant CUX1 expression increased tumour cell proliferation, tumour growth, resistance to apoptosis, and angiogenesis in vitro and in vivo. Mechanistically, the pro-angiogenic effect of CUX1 was mediated via upregulation of effectors such as HIF1α and MMP9. CUX1 mediates an invasive pro-angiogenic phenotype and is associated with malignant behaviour in human insulinomas.
journal_name
Endocr Relat Cancerjournal_title
Endocrine-related cancerauthors
Krug S,Kühnemuth B,Griesmann H,Neesse A,Mühlberg L,Boch M,Kortenhaus J,Fendrich V,Wiese D,Sipos B,Friemel J,Gress TM,Michl Pdoi
10.1530/ERC-14-0152subject
Has Abstractpub_date
2014-01-01 00:00:00pages
879-90issue
6eissn
1351-0088issn
1479-6821pii
ERC-14-0152journal_volume
21pub_type
杂志文章abstract::Evidence supports a role of 17&-estradiol (E2) in carcinogenesis and the large majority of breast carcinomas are dependent on estrogen. The anti-estrogen tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer; however, it is also carcinogenic in human uterus and rat liver, highlighting the p...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0078
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abstract::Insulinomas are rare endocrine neoplasias that constitute the most frequent islet cell tumours. Somatostatin (SST) analogs are tentatively used to inhibit insulin secretion and control tumour growth in patients with local invasion or inoperative metastasis, but variable responses have been reported. Data regarding som...
journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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doi:10.1530/ERC-18-0314
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-10-0109
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journal_title:Endocrine-related cancer
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abstract::FOXE1 is a thyroid-specific transcription factor essential for thyroid gland development and maintenance of the differentiated state. Interestingly, a strong association has been recently described between FOXE1 expression and susceptibility to thyroid cancer, but little is known about the mechanisms underlying FOXE1-...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-16-0525
更新日期:2017-05-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/ERC-07-0188
更新日期:2008-03-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-17-0121
更新日期:2017-08-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-11-0136
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journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
doi:10.1530/ERC-14-0516
更新日期:2015-02-01 00:00:00
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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
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
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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 competi...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1677/erc.1.00905
更新日期:2005-12-01 00:00:00
abstract::Genetic alteration is the driving force for thyroid tumorigenesis and progression, based upon which novel approaches to the management of thyroid cancer can be developed. A recent important genetic finding in thyroid cancer is the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf kinase, BRAF...
journal_title:Endocrine-related cancer
pub_type: 杂志文章,评审
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更新日期:2005-06-01 00:00:00
abstract::Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation disco...
journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-16-0141
更新日期:2016-12-01 00:00:00
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journal_title:Endocrine-related cancer
pub_type: 杂志文章
doi:10.1530/ERC-14-0269
更新日期:2015-04-01 00:00:00
abstract::The etiology and pathogenesis of renal cell carcinoma (RCC) are only partially understood. Key findings in hereditary RCC, which may be site specific or a component of a syndrome, have contributed to our current understanding. Important heritable syndromes of RCC are those associated with pheochromocytoma, especially ...
journal_title:Endocrine-related cancer
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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:2005-09-01 00:00:00
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journal_title:Endocrine-related cancer
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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,评审
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更新日期:2009-03-01 00:00:00