Abstract:
:Studies have shown that the calcium-sensing receptor (CaSR) mediates the antitumorigenic effects of calcium against colorectal cancer (CRC). Expression of the CaSR in colorectal tumors is often reduced. We have reported previously that silencing of CaSR in CRC is caused in part by methylation of CaSR promoter 2 and loss of histone acetylation. We investigated the impact of aberrant microRNA expression on loss of CaSR expression. A microarray study in two Caco-2 subclones (Caco2/AQ and Caco2/15) that have similar genetic background, but different CaSR expression levels (Caco2/AQ expressing more CaSR than Caco2/15), identified 22 differentially expressed microRNAs that potentially target the CaSR. We validated these results by performing gain- and loss-of-function studies with the top candidates: miR-9, miR-27a, miR-135b, and miR-146b. Modulation of miR-135b or miR-146b expression by mimicking or inhibiting their expression regulated CaSR protein levels in two different colon cancer cell lines: Caco2/AQ (moderate endogenous CaSR expression) and HT29 (low endogenous CaSR levels). Inhibition of miR-135b and miR-146b expression led to high CaSR levels and significantly reduced proliferation. In samples of colorectal tumors we observed overexpression of miR-135b and miR-146b, and this correlated inversely with CaSR expression (miR-135b: r = -0.684, p < 0.001 and miR-146b: r = -0.448, p < 0.001), supporting our in vitro findings. We demonstrate that miR-135b and miR-146b target the CaSR and reduce its expression in colorectal tumors, reducing the antiproliferative and prodifferentiating actions of calcium. This provides a new approach for finding means to prevent CaSR loss, developing better treatment strategies for CRC.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Fetahu IS,Tennakoon S,Lines KE,Gröschel C,Aggarwal A,Mesteri I,Baumgartner-Parzer S,Mader RM,Thakker RV,Kállay Edoi
10.1002/ijc.29681subject
Has Abstractpub_date
2016-01-01 00:00:00pages
137-45issue
1eissn
0020-7136issn
1097-0215journal_volume
138pub_type
杂志文章abstract::The causes of childhood cancers are largely unknown. Birth order has been used as a proxy for prenatal and postnatal exposures, such as frequency of infections and in utero hormone exposures. We investigated the association between birth order and childhood cancers in a pooled case-control dataset. The subjects were d...
journal_title:International journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1002/ijc.25593
更新日期:2011-06-01 00:00:00
abstract::BALB/c and C3H- mice were given a single injection of methylcholanthrene (MCA) and were tested at various times thereafter for immunologic reactivity and resistance to syngeneic tumor challenge. MCA treatment did not affect the rejection of H-2-incompatible tumor allografts, the rejection of H-2-compatible skin allogr...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910210418
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abstract::Gain of chromosome 1q is a hallmark of breast cancer, and likely reflects oncogene amplification. We previously identified mitotic kinesin KIF14 (kinesin family member 14) as an overexpressed candidate oncogene in the 1q31.3-1q32.1 minimal region of genomic gain in breast cancer cell lines. KIF14 also showed high expr...
journal_title:International journal of cancer
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doi:10.1002/ijc.21954
更新日期:2006-09-01 00:00:00
abstract::As many patients with mammary carcinoma are now treated by conservative forms of surgery, there is a need for prognostic information obtainable from the primary tumour alone. One possible source is the antigenic profile of tumour cells. Using an indirect immunoperoxidase technique, we stained histological sections of ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910330304
更新日期:1984-03-15 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章,评审
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更新日期:2005-03-01 00:00:00
abstract::Hybrid Capture 2 (HC2) Human Papillomavirus (HPV) DNA Test® is FDA approved and is a proven aid in detecting HPV infections of the cervix and as an aid in diagnosing, with cytology, cervical disease. A prospective feasibility study was conducted to determine if HC2 testing has utility when screening for high-grade ana...
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abstract::Secreted frizzled-related proteins (SFRPs) are antagonists of the Wnt signaling pathway whose epigenetic downregulation have been shown to be involved in hepatocarcinogenesis. However, dysregulation of SFRPs induced by hepatitis B virus (HBV) X protein (HBx) has never been studied in HBV-related hepatocellular carcino...
journal_title:International journal of cancer
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abstract::Oncostatin M is a leukocyte product that has been reported to have anti-proliferative effects directly on melanoma and other cancer cell lines in vitro. However, its function(s) in cancers in vivo appears complex and its roles in cancer growth in lungs are unknown. Here, we show that OSM promotes marked growth of tumo...
journal_title:International journal of cancer
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doi:10.1002/ijc.29055
更新日期:2015-02-15 00:00:00
abstract::Overuse of antibiotic drugs alters the composition of gut microbiota and has detrimental effects on the host. In our study, we investigated association of gut flora and antibiotics in the prognosis of patients with liver cancer who have undergone chemotherapy by analyzing two independent clinical studies. We retrospec...
journal_title:International journal of cancer
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abstract::Clinical and experimental scintigraphic studies have found that radiolabelled antibodies are not only taken up by tumour(s) but also by normal liver. The accumulation of radionuclides in this organ poses a major problem to the use of radiolabelled antibodies as diagnostic and therapeutic tools. In an attempt to unders...
journal_title:International journal of cancer
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abstract::Studies with purified DT-diaphorase have shown that the enzyme is capable of catalyzing a two-electron reduction of the novel indoloquinone EO9 to a DNA-damaging alkylating species. The aim of this study was to determine to what extent DT-diaphorase may be involved in the metabolic activation of EO9 and mitomycin C in...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910560124
更新日期:1994-01-02 00:00:00
abstract::Commercial cow milk contains considerable amounts of estrogens. Our study assessed the effect of commercial low-fat milk on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in rats. Eighty 6-week-old female Sprague-Dawley rats received a single oral dose of 5 mg DMBA. Twenty-four hours l...
journal_title:International journal of cancer
pub_type: 杂志文章
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更新日期:2004-07-01 00:00:00
abstract::Inbred rats were treated with extranuclear tumour membrane fractions or 3 M KCl-solubilized extracts of two antigenically distinct 3-methylcholanthrene-induced sarcomas, Mc7 and Mc57. The rats developed tumour-specific humoral antibody responses, but were not immune to tumour challenge. Moreover, they were unresponsiv...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910180511
更新日期:1976-11-15 00:00:00
abstract::Recent suggestions that tumor-cell targeting of elastin-rich tissues (e.g., lung) correlates with the presence of surface elastin receptors have been investigated. Receptors for insoluble (fibrous) elastin and for soluble elastin peptides have been implemented in these correlations. A rapid assay for binding of insolu...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910530520
更新日期:1993-03-12 00:00:00
abstract::Studies have shown an increased risk of malignancies in women with endometriosis. Little is known about the impact of endometriosis on cancer survival. We investigated whether the survival after a diagnosis of a malignancy differs in women with a previously diagnosed endometriosis compared to other women. Women with a...
journal_title:International journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1002/ijc.25718
更新日期:2011-08-15 00:00:00
abstract::Endostatin, the proteolytic fragment of collagen XVIII, is an inhibitor of angiogenesis and tumor growth. Interestingly, elevated circulating endostatin levels have been found to correlate with poor patients' prognosis in several cancers. The aim of this study was to assess the prognostic value of endostatin in bladde...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26343
更新日期:2012-06-15 00:00:00
abstract::Infection of tumors with an adenoviral vector expressing a chimeric gene composed of the CArG elements of the Egr-1 promoter and a cDNA encoding TNF-alpha (Ad.Egr-TNF) has previously been shown to result in the production of high intratumoral levels of TNF-alpha and thereby tumor regression. The antitumor effects of T...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1629
更新日期:2002-02-01 00:00:00
abstract::Phenotypic and functional characteristics of tumor-infiltrating lymphocytes (TIL) obtained from human primary and metastatic liver tumors were studied. Lymphocytes isolated from 18 tumors and autologous (A) peripheral blood (6 cases) were phenotyped by 2-color flow cytometry and cloned in a limiting dilution system, w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460521
更新日期:1990-11-15 00:00:00
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19970328)71:1<20::aid-ijc5
更新日期:1997-03-28 00:00:00
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journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910200505
更新日期:1977-11-15 00:00:00
abstract::In an attempt to obtain cell lines from the different components found in primary breast cancers, we used a low-calcium medium to culture epithelial cells of mixed phenotype and a recombinant T antigen containing retrovirus to immortalize cells found in these cultures. In each case, the histology of the sample used fo...
journal_title:International journal of cancer
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doi:10.1002/ijc.2910510417
更新日期:1992-06-19 00:00:00
abstract::Cholera toxin (which increases intracellular cAMP levels) significantly (p less than 0.05) increased the growth of MCF-7, T47-D and Hs578T human breast carcinoma cells in vitro. The effect of cholera toxin on growth of MCF-7 and T47-D cells was more pronounced in the presence of 17 beta-estradiol (p less than 0.05), i...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910360411
更新日期:1985-10-15 00:00:00
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journal_title:International journal of cancer
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abstract::Liquid-based cytology (LBC) has replaced conventional cytology (CC) for cervical cancer screening in some countries. However, it remains unclear whether LBC is superior to CC. A randomized controlled trial was conducted between August 2007 and March 2009 in Germany to compare LBC, alone and in combination with compute...
journal_title:International journal of cancer
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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doi:10.1002/ijc.2910370514
更新日期:1986-05-15 00:00:00
abstract::In order to study the mechanisms responsible for resistance to CDDP, 5 human tumor cell lines were made resistant to CDDP by repeated in vitro exposures. After cloning it was found that the cell lines developed were between 3.3-fold and 17-fold more resistant to CDDP than the parental cell lines at the IC90. These lin...
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更新日期:1991-01-21 00:00:00