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RNA helicase DDX20 as a surrogate marker of statin activity in invasive breast cancer

中国药理学与毒理学杂志 2015年第S1期29卷 84-84页

作者： ChaoWANG BeiyingQIU JeanPaulTHIERY GautamSETHI PatrickJ.CASEY CelestialT.YAP SooChinLEE VinayTERGAONKAR AlanPremKUMAR Cancer Science Institute of Singapore National University of Singapore Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Institute of Molecular and Cell biology ASTAR Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore National University Cancer Institute of Singapore Duke-NUS Graduate Medical School Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Department of Haematology-Oncology National University Hospital Singapore Department of Biological Sciences University of North Texas

OBJECTIVE To evaluate if RNA helicase DDX20,highly expressed in triple negative breast cancer(TNBC)cells,could serve as a surrogate marker for simvastatin treatment *** We first assessed correlation between 17 mevalonate pathway-related genes and expression of DDX20 in a cohort of 1325 breast cancer *** cells,MDA-MB-231,were then treated with simvastatin and mevalonate pathway intermediates to assess the alteration in DDX20 *** the mouse model,MDA-MB-231 cells were injected to tail veins of mice,groups of 8mice each were injected intraperioneally with vehicle or simvastatin 25mg·kg-1 3times a week for *** number of metastatic colonies formed was quantified and immunohistochemical(IHC)staining of DDX20 was carried out in the lung *** Among the 17 genes evaluated,positive correlation with DDX20 expression was observed in eight of them,with HMGCR having the highest *** in vitro experiments show exposure of breast cancer cells to simvastatin lead to a Rho-dependent decrease in gene expression of DDX20,leading to decreased tumor proliferation in a mevalonate pathway-dependent ***,ectopic overexpression of DDX20 significantly abrogated the anti-metastatic activity of simvastatin.A similar observation is seen in the mouse model,where simvastatin-injected mice show significantly fewer visible lung metastases compared to placebo-fed *** staining on these lung tissues showed decreased DDX20 expression in simvastatin-injected group,corroborating our observations in *** DDX20 is a potential surrogate marker for simvastatin treatment response in breast cancer and a long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using statins(to suppress DDX20 gene expression)and a suitable firstline agent″for the kill″of invasive breast cancer.

关键词： RNA helicase DDX20 surrogate marker simvastatin br

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experimental Researches on Carcinogenesis or tumorigenicity of MDCK Canine Kidney Cell(CKC) Lines and Analysis of Their Chromosome Karyotypes

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Agricultural Sciences in China 2002年第7期1卷 816-827页

作者： ZHANG De-li, LI Liu-jin, XIA Geng-tian, HE Xu-yu, GAO Bu-xian, BAI Xiao-hong, HUANG Gao-sheng, LIU Shang-gao, YAN Long-fei and FANG Fu-de( Department of Immunology, School of Basic Medical Sciences , Peking University Health Science Center , Beijing 100083 , P. R . China Beijing Institute of Preventive Medicine , Beijing 100071 , P. R . China Department of Toxicology at Center for Research & Development of Animal Healthcare Products , Fourth Military Medical University , Xian 710032 , P. R . China Department of Pathology at School of Pre-clinical Education , Section of Pathology at Xi-Jing Hospital, Institute for Cancer Research at China Cancer Research Foundation , Fourth Military Medical University, Xian 710032 , P. R . China Key Open Laboratory of Preventive Veterinary Medicine of State Ministry of Agriculture, College of Animal Medical Sciences & State Key Laboratory of Agricultural Biotechnology , College of Biological Sciences , China Agricultural University , Beijing 100094 , P.R.China State Key Laboratory of Medical Molecular biology, School of Basic Medical Sciences at the Peking Union Medical Colloge /Institute of Basic Medical Sciences at the Chinese Academy of Medical Sciences , Beijing 100005 , P. R . China) Department of Immunology School of Basic Medical Sciences Peking University Health Science Center Beijing 100083 P. R.China Beijing Institute of Preventive Medicine Beijing 100071P.R.China Department of Pathology at School of Pre-clinical Education Department of Toxicology at Center for Research Development of Animal Healthcare Products Fourth Military Medical University Xian 710032 P. R . China Beijing Institute of Preventive Medicine Beijing 100071P.R.China Department of Pathology at School of Pre-clinical Education Section of Pathology at Xi-Jing Hospital Institute for Cancer Research at China Cancer Research Foundation Fourth Military Medical University Xian 710032 P. R . China Key Open Laboratory of Preventive Veterinary Medicine of State Ministry of Agriculture College of Animal Medical Sciences State Key Laboratory of Agricultural Biotechnology College of Biological Sciences China Agricultural University Beijing 100094 P State Key Laboratory of Medical Molecular biology School of Basic Medical Sciences at the Peking Union Medical Colloge/Institute of Basic Medical Sciences at the Chinese Academy of Medical Sciences Beijing 100005 P.R. China

The chromosomal number variations & structural aberrations of the MDCK cell line, primary feline or canine kidney cell(FKC or CKC) and Hela cell line were investigated and their karyotypes of conventional chromosome bands were analyzed. The carcinogenesis or tumorigenicity testing of these cell lines in about 232 nude mice and for colony formation in soft agarose and for haemagglutination under different concentration of plant lectins of these cells were carried out. Under the prerequisite that the incidence of cancer or tumor in negative-control nude mice inoculated subcutaneously with primary feline or canine kidney cell cultures purified in vitro at passage 3 was 0 (0/22) and 0 (0/10), respectively. The incidence of the progressively-growing malignant tumor(MT) in positive-control nude mice inoculated subcutaneously with Hela cell cultures of KB, X, or NM20/X strain was 10/10, 25/25 and 5/51, respectively. The results showed that the incidence of tumor in nude mice with tetraploid YA strain of MDCK cell during 20 - 45 passages, with hy-podiploid JB strain of MDCK cell on passage 25, with di-and hypoploid JC strain of MDCK cell during 2-15 passages or with hypoploid M strain of MDCK cell during 9 - 27 passages was 28/58, 1/5, 4/18 and 0/31, respectively. The chromosomal analysis results showed that the ratio of difference in the rate of modal chromosome number between high(mcs+ n) and lowest (mcs) passages was not more than 5% - 15% and the structure aberrations was generally 0 - 3% . These results proved that the genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species-specific. MDCK line has tumorigenicity no matter what its chromosome karyotype is, at least it has very low tumorigenicity even when its modal chromosome number is hypoploid. The repeatedly frozen, thawed and split controls of tumorigenicity-positive cell lines(X strain of Hela, M strain of BHK-21, JA strain of Vero, YA strain of MDCK) have much

关键词： Cell line MDCK Hela Feline or canine kidney cell Karyotypes Carcinogenesis or tuniori-genicity

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Breast Cancer Risk Genes-Association Analysis in More than 113,000 Women

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四川生理科学杂志 2021年第1期43卷 7-7页

作者： Leila Dorling The authors' affiliations are as follows: the Centre for Cancer Genetic Epidemiology Departments of Public Health and Primary Care (L.D. S. Carvalho J.A. K.A.P. Q.W. M.K.B. J.D. B.D. N. Mavaddat K. Michailidou A.C.A. P.D.P.P. D.F.E.) and Oncology (C.L. P.A.H. C. Baynes D.M.C. L.F. V.R. M. Shah P.D.P.P. A.M.D. D.F.E.) University of Cambridge Cambridge the Centre for Genomic and Experimental Medicine MRC Institute of Genetics and Molecular Medicine (A. Campbell D.J.P.) and the Centre for Cognitive Ageing and Cognitive Epidemiology Department of Psychology (D.J.P.) University of Edinburgh the Cancer Research UK Edinburgh Centre (D.A.C. J.F.) and the Usher Institute of Population Health Sciences and Informatics University of Edinburgh Medical School (A. Campbell J.F.) Edinburgh the Divisions of Informatics Imaging and Data Sciences (E.F.H.) Cancer Sciences (A. Howell) Population Health Health Services Research and Primary Care (A. Lophatananon K. Muir) and Evolution and Genomic Sciences School of Biological Sciences (W.G.N. E.M.V. D.G.E.) University of Manchester the NIHR Manchester Biomedical Research Unit (E.F.H.) and the Nightingale Breast Screening Centre Wythenshawe Hospital (E.F.H. H.I.) Academic Health Science Centre and North West Genomics Laboratory Hub and the Manchester Centre for Genomic Medicine St. Mary's Hospital Manchester University NHS Foundation Trust (W.G.N. E.M.V. D.G.E.) Manchester the School of Cancer and Pharmaceutical Sciences Comprehensive Cancer Centre Guy's Campus King's College London London (E.J.S.) the Institute of Cancer and Genomic Sciences University of Birmingham Birmingham (I.T.) and the Wellcome Trust Centre for Human Genetics and Oxford NIHR Biomedical Research Centre University of Oxford Oxford (I.T.) - all in the United Kingdom the Human Genotyping-CEGEN Unit Human Cancer Genetic Program (A.G.-N. M.R.A. N.Á. B.H. R.N.-T.) and the Human Genetics Group (V.F. A.O. J.B.) Spanish National Cancer Research

Background:Genetic testing for breast cancer susceptibility is widely used,but for many genes,evidence of an association with breast cancer is weak,underlying risk estimates are imprecise,and reliable subtype-specific risk estimates are ***:We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 *** separate analyses for protein-truncating variants and rare missense variants in these genes,we estimated odds ratios for breast cancer overall and tumor *** evaluated missense-variant associations according to domain and classification of pathogenicity.

关键词： cancer Breast Cancer

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