Abstract:
BACKGROUND:Pancreatic cancer is highly malignant and characterised by rapid and uncontrolled growth. While some of the important regulatory networks involved in pancreatic cancer have been determined, the cancer relevant genes have not been fully identified. METHODS:We screened genes that may control proliferation in pancreatic cancer in seven pairs of matched pancreatic cancer and normal pancreatic tissue samples. We examined KIF15 expression in pancreatic cancer tissues and the effect of KIF15 on cell proliferation in vitro and in vivo. The mechanisms underlying KIF15 promotion of cell proliferation were investigated. RESULTS:mRNA microarray and functional analysis identified 22 genes that potentially play an important role in the proliferation of pancreatic cancer. High-content siRNA screening evaluated whether silencing these 22 genes affected proliferation of pancreatic cancer. Notably, silencing KIF15 exhibited the most potent inhibition of proliferation compared with the rest of the 22 genes. KIF15 was upregulated in human pancreatic cancer tissues, and higher KIF15 expression levels correlated with shorter patient survival times. Upregulation KIF15 promoted pancreatic cancer growth. KIF15 upregulated cyclin D1, CDK2, and phospho-RB and also promoted G1/S transition in pancreatic cancer cells. KIF15 upregulation activated MEK-ERK signalling by increasing p-MEK and p-ERK levels. MEK-ERK inhibitors successfully inhibited cell cycle progression, and PD98059 blocked KIF15-mediated pancreatic cancer proliferation in vivo and in vitro. CONCLUSIONS:This study identified KIF15 as a critical regulator that promotes pancreatic cancer proliferation, broadening our understanding of KIF15 function in tumorigenesis.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Wang J,Guo X,Xie C,Jiang Jdoi
10.1038/bjc.2017.165subject
Has Abstractpub_date
2017-07-11 00:00:00pages
245-255issue
2eissn
0007-0920issn
1532-1827pii
bjc2017165journal_volume
117pub_type
杂志文章abstract::We have shown previously that the relative expression of a truncated oestrogen receptor-alpha variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-d...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690156
更新日期:1999-02-01 00:00:00
abstract::Elderly patients are recommended to have a reduced starting dose (300 mg m(-2) once every 3 weeks) of irinotecan monotherapy. The aims of this analysis are to compare toxicity and survival according to age, performance status (PS), gender and prior radical pelvic radiotherapy (RT). The primary end points were overall ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/sj.bjc.6602169
更新日期:2004-10-18 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
abstract::Pleural effusion fluid obtained from eleven patients with metastatic spread to the pleura was screened for the ability to cause the dispersal--'scattering'--of MDCK colonies in vitro. Four of these samples proved to be positive using this assay. Of these two had titres high enough to warrant further purification on a ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.251
更新日期:1992-08-01 00:00:00
abstract::It has recently been reported that a series of testis cancers shows a temporal cycle in birth dates with a peak in certain months. This observation has been tested by an examination of a larger series covering all testis cancers diagnosed in the years 1971-84 in England and Wales, in men born in 1940 or later. Limited...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.117
更新日期:1987-05-01 00:00:00
abstract::Epstein-Barr virus (EBV) expression was investigated by immunohistochemistry (latent membrane protein 1 [LMP-1]) and in situ hybridization (EBV encoded RNA [EBER]) in biopsies from 95 patients with untreated Hodgkin's disease (HD). Tumour EBV status was related to EBV antibody titres, spontaneous and concanavalin A in...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690827
更新日期:1999-12-01 00:00:00
abstract::5-fluorouracil (5FU) is activated intracellularly to cytotoxic 5-fluoronucleotides (FNuct). These were detected non-invasively in rats bearing the Walker carcinosarcoma by 19F-magnetic resonance spectroscopy (MRS) following an i.v. bolus dose of 5FU (50 mg kg-1). Pre-treatment of the rats (3 to 24 h earlier) by methot...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.75
更新日期:1992-03-01 00:00:00
abstract::Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very li...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.258
更新日期:1998-05-01 00:00:00
abstract::Using a recently developed model for studying the biology of locally recurrent (LR) mammary tumours in the 13762NF rat mammary adenocarcinoma system, we examined the sensitivity to polymorphonuclear cell, macrophage and natural killer cell cytolysis. The parental MTF7(T20) cell line; the 'primary' tumours which arose ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.302
更新日期:1988-12-01 00:00:00
abstract::Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.174
更新日期:1980-06-01 00:00:00
abstract::Serum concentrations of oestradiol-17β were measured by radio-immunoassay during 40 menstrual cycles from 38 normal premenopausal women. Repeated samples were studied from 25 normal postmenopausal women. The method was highly specific and extremely sensitive. In premenopausal women the pattern of serum oestradiol-17β ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.98
更新日期:1974-06-01 00:00:00
abstract::1,25(OH)2D3 promotes differentiation and has an antiproliferative effect in a variety of cell lines derived from the immunohaematopoetic system. alpha-Calcidol which is metabolised to 1,25(OH)2D3 has been shown to produce tumour regression in follicular low grade non-Hodgkin's lymphoma (NHL) and the dose limiting toxi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.406
更新日期:1993-10-01 00:00:00
abstract:BACKGROUND:RECORD-3 assessed non-inferiority of progression-free survival (PFS) with everolimus vs sunitinib in previously untreated patients with metastatic renal cell carcinoma. Baseline plasma sample collection and randomised design enabled correlation of circulating biomarkers with efficacy. METHODS:Samples were a...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2016.21
更新日期:2016-03-15 00:00:00
abstract::Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use. This represents a random sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 (excluding 1980 and 1981) with a 100% follow-up. Ever-us...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690543
更新日期:1999-07-01 00:00:00
abstract::The sera from patients with advanced cancer were tested for their specific inhibitory effects on the cytotoxicity of autologous lymphocytes on tumour cells in a microculture assay. By adding a standard volume of the sera to suspensions of well-washed lymphocytes the inhibitory effect was quantitated by comparison with...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.67
更新日期:1973-07-01 00:00:00
abstract:BACKGROUND:The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS:Two cohorts were compared: one was a group with young-onset PrCa, t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605822
更新日期:2010-09-07 00:00:00
abstract::The WWOX (WW-domain containing oxidoreductase) is a candidate tumour suppressor gene spanning the same chromosome region, 16q23, as the second most common fragile site (FS), FRA16D. Deletions detected by comparative genomic hybridisation (CGH) and loss of heterozygosity at microsatellite markers on chromosome 16q are ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602023
更新日期:2004-08-16 00:00:00
abstract::The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.47
更新日期:1977-03-01 00:00:00
abstract::The conventional diffusion chamber (CDC) as described by Benestad (1970) had been modified to assay the colony forming capacity of RFM bone marrow and spleen cells in agar diffusion chambers (ADCs). The colonies are morphologically identical to those formed by the CFUc in agar culture in vitro and have an incidence of...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1974.216
更新日期:1974-11-01 00:00:00
abstract::In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to the...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.159
更新日期:1983-07-01 00:00:00
abstract::Two policies of palliative thoracic radiotherapy for non-small-cell lung cancer have been compared in a randomised multicentre controlled trial. A total of 369 patients with inoperable, histologically or cytologically confirmed disease, too advanced for radical 'curative' radiotherapy, and with their main symptoms rel...
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/bjc.1991.62
更新日期:1991-02-01 00:00:00
abstract::In clinically organ-confined prostate cancer patients, bloodstream tumour cell dissemination generally occurs, and may be enhanced by surgical prostate manipulation. To evaluate cancer-cell seeding impact upon patient recurrence-free survival, 155 patients were prospectively enrolled then followed. Here, 57 patients p...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604912
更新日期:2009-02-24 00:00:00
abstract::Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2162
更新日期:2001-11-30 00:00:00
abstract::We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements wer...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602916
更新日期:2006-01-16 00:00:00
abstract::We analysed two case-control studies of women from Italy and Switzerland, including 195 cases of oral and pharyngeal cancers and 1113 controls. The multivariate odds ratio was 4.6 for heavy smokers and 2.7 for high alcohol intake. Vegetables, fruit, beta-carotene and wholegrain foods were inversely, butter and retinol...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.0900
更新日期:2000-01-01 00:00:00
abstract::Serum levels of cell-free interleukin-2 receptors were elevated above normal in mice bearing the IL-2R positive T-cell lymphoma Eb or its highly metastatic variant ESb. Although ESb cells expressed less IL-2R molecules than Eb cells on their cell surface, serum receptor levels were raised more quickly in ESb than in E...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.119
更新日期:1987-06-01 00:00:00
abstract::The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutatio...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1054/bjoc.2001.2128
更新日期:2001-12-14 00:00:00
abstract::Following relapse on endocrine therapy for advanced, hormone receptor-positive breast cancer, it is common for patients to experience responses to alternative endocrine agents. Fulvestrant ('Faslodex') is a new type of endocrine treatment--an oestrogen receptor (ER) antagonist with no agonist effects. Fulvestrant down...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6601632
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:This study aims to investigate the association between statin use and all-cancer survival in a prospective cohort of postmenopausal women, using data from the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT). METHODS:The WHI study enrolled women aged 50-79 years from 1993 t...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2016.149
更新日期:2016-06-28 00:00:00
abstract::Between 1980 and 1985, 914 patients with head and neck squamous cell carcinoma underwent lymph node dissection in our institution. The prognostic value of clinical factors has already been reported (Mamelle et al, 1994, Am J Surg 168: 494-498). We present here a comparison of biological characteristics of pharyngeal t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.320
更新日期:1998-06-01 00:00:00