Abstract:
BACKGROUND:Inhibitors of the mammalian target of rapamycin (mTOR) might become a novel tool to treat advanced prostate cancer. However, chronic drug exposure may trigger resistance, limiting the utility of mTOR inhibitors. METHODS:Metastatic potential of PC3 prostate cancer cells, susceptible (PC3(par)) or resistant (PC3(res)) to the mTOR-inhibitor RAD001 was investigated. Adhesion to vascular endothelium or immobilised collagen, fibronectin and laminin was quantified. Motility, migration and invasion were explored by modified Boyden chamber assay. Integrin α and β subtypes were analysed by flow cytometry, western blotting and real-time PCR. Integrin-related signalling, EGFr, Akt, p70S6kinase and ERK1/2 activation were determined. RESULTS:Adhesion was reduced, whereas motility, migration and invasion were enhanced in PC3(res). The α2 and β1 integrin subtypes were dramatically elevated, integrins α1 and α6 were lowered, whereas α5 was nearly lost in PC3(res). Activation of the Akt signalling pathway was strongly upregulated in these cells. Treating PC3(par) cells with RAD001 reduced motility, migration and invasion and deactivated Akt signalling. Blocking studies revealed that α2 and β1 integrins significantly trigger the motile behaviour of the tumour cells. CONCLUSION:Chronic RAD001 treatment caused resistance development characterised by distinct modification of the integrin-expression profile, driving prostate cancer cells towards high motility.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Tsaur I,Makarević J,Juengel E,Gasser M,Waaga-Gasser AM,Kurosch M,Reiter M,Wedel S,Bartsch G,Haferkamp A,Wiesner C,Blaheta RAdoi
10.1038/bjc.2012.313subject
Has Abstractpub_date
2012-08-21 00:00:00pages
847-55issue
5eissn
0007-0920issn
1532-1827pii
bjc2012313journal_volume
107pub_type
杂志文章abstract::MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6605901
更新日期:2010-10-12 00:00:00
abstract::Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then mont...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/sj.bjc.6600588
更新日期:2002-10-21 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.528
更新日期:1998-08-01 00:00:00
abstract::We identified 2384 patients in the Danish Cancer Register in whom cancer had been diagnosed in 1960-1996 before they reached the age of 20 and compared them with 53 143 sex- and age-matched controls identified from the Register of Population Statistics. Complete education records and demographic and socioeconomic info...
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doi:10.1038/sj.bjc.6602085
更新日期:2004-08-31 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:1998-10-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1998-07-01 00:00:00
abstract::In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.207
更新日期:1994-06-01 00:00:00
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pub_type: 杂志文章
doi:10.1038/s41416-020-0964-x
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abstract::We have studied whether N-methylformamide can affect the expression pattern of adhesion molecules and the attachment behaviour of M14 human melanoma cells. The role of N-methylformamide on experimental and spontaneous pulmonary metastases from M14 cells in nude mice was also investigated. We demonstrate that N-methylf...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.35
更新日期:1998-01-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1983-09-01 00:00:00
abstract::The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction. Twelve chemonaive patients with ovarian cancer were treated w...
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2001-01-05 00:00:00
abstract::An antigen common to human sarcomas, S3, has been further characterized. It is antigenically distinct from human blood-group substances A and B and from heterophile antigens such as Forssman, infectious mononucleosis and serum sickness antigens. Whilst S3 antigen preparations may contain small amounts of CEA and AFP t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.43
更新日期:1981-03-01 00:00:00
abstract::Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resista...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.339
更新日期:1990-10-01 00:00:00
abstract::We conducted a national, retrospective population-based cohort study of 705 patients hospitalized with a first diagnosis of dermatomyositis (DM) or polymyositis (PM) during 1982-1996 based on linkage of hospital discharge, cancer registration, and death records in Scotland. Risks of cancer were assessed by calculating...
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.423
更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2018-04-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1997-01-01 00:00:00
abstract::The objective of the study was to review the natural history of patients with a malignant pleural effusion but without obvious evidence of a primary, to assess the value of investigations used to look for a primary and to assess the response to palliative chemotherapy. This was done by a retrospective study of patient...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.444
更新日期:1996-09-01 00:00:00
abstract::The present study set out to evaluate perceptions of risk, psychological morbidity and health behaviours in women with a family history of breast cancer who have attended genetic counselling and determine how these differ from general population risk women. Data were collected from 62 genetic counselees (cases) attend...
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pub_type: 杂志文章
doi:10.1038/bjc.1996.387
更新日期:1996-08-01 00:00:00
abstract::Increased 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) uptake is the most commonly used marker for positron emission tomography in oncology. However, a proliferation tracer such as 3'-deoxy-3'-[18F]fluorothymidine (FLT) might be more specific for cancer. 3'-deoxy-3'-[18F]fluorothymidine uptake is dependent on thymidine kin...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604523
更新日期:2008-08-05 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.1987.163
更新日期:1987-08-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602630
更新日期:2005-06-20 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:2014-02-04 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601776
更新日期:2004-05-17 00:00:00
abstract::Seventy three children with rhabdomyosarcoma were treated by members of the Children's Solid Tumour Group during the period, 1974-1981. The extent of disease at diagnosis was found to be the major influence affecting outcome. Children with tumours confined to the tissue of origin with no evidence of nodal or metastati...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.175
更新日期:1983-08-01 00:00:00