Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer

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Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer


نویسنده	maxwell c.a. ,benítez j. ,gómez-baldó l. ,osorio a. ,bonifaci n. ,fernández-ramires r. ,costes s.v. ,guinó e. ,chen h. ,evans g.j.r. ,mohan p. ,català i. ,petit a. ,aguilar h. ,villanueva a. ,aytes a. ,serra-musach j. ,rennert g. ,lejbkowicz f. ,peterlongo p. ,manoukian s. ,peissel b. ,ripamonti c.b. ,bonanni b. ,viel a. ,allavena a. ,bernard l. ,radice p. ,friedman e. ,kaufman b. ,laitman y. ,dubrovsky m. ,milgrom r. ,jakubowska a. ,cybulski c. ,gorski b. ,jaworska k. ,durda k. ,sukiennicki g. ,lubiński j. ,shugart y.y. ,domchek s.m. ,letrero r. ,weber b.l. ,hogervorst f.b.l. ,rookus m.a. ,collee j.m. ,devilee p. ,ligtenberg m.j. ,van der luijt r.b. ,aalfs c.m. ,waisfisz q. ,wijnen j. ,van roozendaal c.e.p. ,hebon hereditary breast and ovarian cancer group ,embrace centre for cancer genetic epidemiology ,easton d.f. ,peock s. ,cook m. ,oliver c. ,frost d. ,harrington p. ,lalloo f. ,eeles r. ,izatt l. ,chu c. ,eccles d. ,douglas f. ,brewer c. ,nevanlinna h. ,heikkinen t. ,couch f.j. ,wang x. ,lindor n.m. ,godwin a.k. ,caligo m.a. ,lombardi g. ,loman n. ,karlsson p. ,ehrencrona h. ,von wachenfeldt a. ,swe-brca swedish breast cancer study ,barkardottir r. ,hamann u. ,rashid m.u. ,lasa a. ,caldés t. ,andrés r. ,schmitt m. ,assmann v. ,stevens k. ,offit k. ,curado j. ,tilgner h. ,guigó r. ,aiza g. ,brunet j. ,martrat g. ,urruticoechea a. ,blanco i. ,tihomirova l. ,goldgar d.e. ,buys s. ,john e.m. ,miron a. ,southey m. ,daly m.b. ,bcfr breast cancer family registry ,schmutzler r.k. ,wappenschmidt b. ,meindl a. ,arnold n. ,deissler h. ,varon-mateeva r. ,sutter c. ,niederacher d. ,imyamitov e. ,sinilnikova o.m. ,sinilnikova o.m. ,stoppa-lyonne d. ,mazoyer s. ,verny-pierre c. ,castera l. ,de pauw a. ,bignon y.-j. ,uhrhammer n. ,peyrat j.-p. ,vennin p. ,ferrer s. ,collonge-rame m.-a. ,mortemousque i. ,gemo study collaborators gemo study ,spurdle a.b. ,beesley j. ,chen x. ,healey s. ,barcellos-hoff m.h. ,barcellos-hoff m.h. ,gruber s.b. ,lázaro c. ,capellá g. ,mcguffog l. ,nathanson k.l. ,chenevix-trench g. ,fleisch m.c. ,moreno v. ,pujana m.a.
منبع	plos biology - 2011 - دوره : 9 - شماره : 11
چکیده	Differentiated mammary epithelium shows apicobasal polarity,and loss of tissue organization is an early hallmark of breast carcinogenesis. in brca1 mutation carriers,accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that brca1 regulates stem/progenitor cell proliferation and differentiation. however,the function of brca1 in this process and its link to carcinogenesis remain unknown. here we depict a molecular mechanism involving brca1 and rhamm that regulates apicobasal polarity and,when perturbed,may increase risk of breast cancer. starting from complementary genetic analyses across families and populations,we identified common genetic variation at the low-penetrance susceptibility hmmr locus (encoding for rhamm) that modifies breast cancer risk among brca1,but probably not brca2,mutation carriers: n = 7,584,weighted hazard ratio (whr) = 1.09 (95% ci 1.02-1.16),ptrend = 0.017; and n = 3,965,whr = 1.04 (95% ci 0.94-1.16),ptrend = 0.43; respectively. subsequently,studies of mcf10a apicobasal polarization revealed a central role for brca1 and rhamm,together with aurka and tpx2,in essential reorganization of microtubules. mechanistically,reorganization is facilitated by brca1 and impaired by aurka,which is regulated by negative feedback involving rhamm and tpx2. taken together,our data provide fundamental insight into apicobasal polarization through brca1 function,which may explain the expanded cell subsets and characteristic tumor type accompanying brca1 mutation,while also linking this process to sporadic breast cancer through perturbation of hmmr/rhamm. © 2011 maxwell et al.

آدرس	translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,department of pediatrics,child and family research institute,vancouver,bc, Canada, human cancer genetics programme,spanish national cancer research centre,madrid,spain,biomedical research centre network for rare diseases, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,biomedical research centre network for epidemiology and public health, Spain, human cancer genetics programme,spanish national cancer research centre,madrid,spain,biomedical research centre network for rare diseases, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,biomedical research centre network for epidemiology and public health,spain,biomarkers and susceptibility unit,catalan institute of oncology,idibell,l'hospitalet,catalonia, Spain, human cancer genetics programme,spanish national cancer research centre,madrid,spain,biomedical research centre network for rare diseases, Spain, life sciences division,lawrence berkeley national laboratory,berkeley,ca, United States, biomedical research centre network for epidemiology and public health,spain,biomarkers and susceptibility unit,catalan institute of oncology,idibell,l'hospitalet,catalonia, Spain, child and family research institute,vancouver,bc, Canada, child and family research institute,vancouver,bc,canada,genetic medicine,manchester academic health sciences centre,central manchester university hospitals nhs foundation trust,manchester, United Kingdom, child and family research institute,vancouver,bc, Canada, department of pathology,university hospital of bellvitge,idibell,l'hospitalet,catalonia, Spain, department of pathology,university hospital of bellvitge,idibell,l'hospitalet,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,biomarkers and susceptibility unit,catalan institute of oncology,idibell,l'hospitalet,catalonia, Spain, chs national cancer control center,department of community medicine and epidemiology,carmel medical center and b. rappaport faculty of medicine,technion,haifa, Israel, chs national cancer control center,department of community medicine and epidemiology,carmel medical center and b. rappaport faculty of medicine,technion,haifa, Israel, unit of molecular bases of genetic risk and genetic testing,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,ifom fondazione istituto firc di oncologia molecolare,milan, Italy, unit of medical genetics,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,milan, Italy, unit of medical genetics,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,milan, Italy, unit of molecular bases of genetic risk and genetic testing,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,ifom fondazione istituto firc di oncologia molecolare,milan,italy,unit of medical genetics,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,milan, Italy, division of cancer prevention and genetics,istituto europeo di oncologia,milan, Italy, division of experimental oncology 1,centro di riferimento oncologico,irccs,aviano, Italy, department of genetics,biology and biochemistry,university of turin,turin, Italy, department of experimental oncology,istituto europeo di oncologia,and consortium for genomics technology (cogentech),milan, Italy, unit of molecular bases of genetic risk and genetic testing,department of preventive and predictive medicine,fondazione irccs istituto nazionale tumori,ifom fondazione istituto firc di oncologia molecolare,milan, Italy, the susanne levy gertner oncogenetics unit,institute of human genetics,chaim sheba medical center,ramat gan,israel,sackler faculty of medicine,tel aviv university,ramat aviv, Israel, the susanne levy gertner oncogenetics unit,institute of human genetics,chaim sheba medical center,ramat gan, Israel, the susanne levy gertner oncogenetics unit,institute of human genetics,chaim sheba medical center,ramat gan, Israel, the susanne levy gertner oncogenetics unit,institute of human genetics,chaim sheba medical center,ramat gan, Israel, the susanne levy gertner oncogenetics unit,institute of human genetics,chaim sheba medical center,ramat gan, Israel, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, international hereditary cancer centre,department of genetics and pathology,pomeranian medical university,szczecin, Poland, unit of statistical genetics,division of intramural research program,national institute of mental health,national institute of health,bethesda,md, United States, abramson cancer center,university of pennsylvania school of medicine,philadelphia,pa, United States, abramson cancer center,university of pennsylvania school of medicine,philadelphia,pa, United States, abramson cancer center,university of pennsylvania school of medicine,philadelphia,pa,united states,novartis institutes for biomedical research,cambridge,ma, United States, family cancer clinic,department of pathology,the netherlands cancer institute,amsterdam, Netherlands, department of epidemiology,the netherlands cancer institute,amsterdam, Netherlands, department of clinical genetics,rotterdam family cancer clinic,erasmus university medical center,rotterdam, Netherlands, department of genetic epidemiology,leiden university medical center,leiden, Netherlands, department of human genetics,radboud university medical center,nijmegen, Netherlands, department of clinical molecular genetics,utrecht university medical center,utrecht, Netherlands, department of clinical genetics,academic medical center,amsterdam, Netherlands, department of clinical genetics,vu university medical center,amsterdam, Netherlands, center for human and clinical genetics,leiden university medical center,leiden, Netherlands, department of clinical genetics,university medical center,maastricht, Netherlands, department of public health and primary care,university of cambridge,cambridge, United Kingdom, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, department of oncology,university of cambridge,cambridge, United Kingdom, genetic medicine,manchester academic health sciences centre,central manchester university hospitals nhs foundation trust,manchester, United Kingdom, the oncogenetics team,the institute of cancer research and royal marsden nhs foundation trust,surrey, United Kingdom, clinical genetics,guy's and st. thomas' nhs foundation trust,london, United Kingdom, yorkshire regional genetics service,st. james's hospital,leeds, United Kingdom, wessex clinical genetics service,princess anne hospital,southampton, United Kingdom, institute of human genetics,centre for life,newcastle upon tyne hospitals nhs trust,newcastle upon tyne, United Kingdom, department of clinical genetics,royal devon and exeter hospital,exeter, United Kingdom, department of obstetrics and gynecology,helsinki university central hospital,helsinki, Finland, department of obstetrics and gynecology,helsinki university central hospital,helsinki, Finland, department of laboratory medicine and pathology,mayo clinic,rochester,mn, United States, department of laboratory medicine and pathology,mayo clinic,rochester,mn, United States, department of medical genetics,mayo clinic,rochester,mn, United States, department of pathology and laboratory medicine,university of kansas medical center,kansas city,ks, United States, section of genetic oncology,department of oncology,university of pisa,and department of laboratory medicine,university hospital of pisa,pisa, Italy, section of genetic oncology,department of oncology,university of pisa,and department of laboratory medicine,university hospital of pisa,pisa, Italy, department of oncology,lund university hospital,lund, Sweden, department of oncology,sahlgrenska university hospital,gothenburg, Sweden, department of genetics and pathology,rudbeck laboratory,uppsala university,uppsala, Sweden, department of oncology,karolinska university hospital,stockholm, Sweden, department of pathology,landspitali-university hospital,reykjavik, Iceland, molecular genetics of breast cancer,deutsches krebsforschungszentrum,heidelberg, Germany, molecular genetics of breast cancer,deutsches krebsforschungszentrum,heidelberg, Germany, genetic service,hospital de la santa creu i sant pau,barcelona,catalonia,spain,department of basic sciences,shaukat khanum memorial cancer hospital and research centre,lahore, Pakistan, molecular oncology laboratory,hospital clínico san carlos,madrid, Spain, medical oncology division,hospital clínico de zaragoza,zaragoza, Spain, department of internal medicine iii,university of rostock,rostock, Germany, center for experimental medicine,institute of tumor biology,university hospital hamburg-eppendorf,hamburg, Germany, department of epidemiology,university of michigan,ann arbor,mi, United States, clinical genetics service,department of medicine,memorial sloan-kettering cancer center,new york,ny, United States, bioinformatics and genomics group,centre for genomic regulation (crg),biomedical research park of barcelona (prbb),barcelona,catalonia, Spain, bioinformatics and genomics group,centre for genomic regulation (crg),biomedical research park of barcelona (prbb),barcelona,catalonia, Spain, bioinformatics and genomics group,centre for genomic regulation (crg),biomedical research park of barcelona (prbb),barcelona,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia, Spain, genetic counseling and hereditary cancer programme,catalan institute of oncology,idibell and girona biomedical research institute (idibgi),catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,genetic counseling and hereditary cancer programme,catalan institute of oncology,idibell and girona biomedical research institute (idibgi),catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia, Spain, genetic counseling and hereditary cancer programme,catalan institute of oncology,idibell and girona biomedical research institute (idibgi),catalonia, Spain, latvian biomedical research and study center,riga, Latvia, department of dermatology,university of utah school of medicine,salt lake city,ut, United States, department of internal medicine,huntsman cancer institute,salt lake city,ut, United States, cancer prevention institute of california,fremont,ca, United States, department of cancer biology,dana-farber cancer institute,and department of surgery,harvard medical school,boston,ma, United States, centre for molecular,environmental,genetic and analytic (mega),epidemiology,melbourne school of population health,the university of melbourne,victoria, Australia, division of population science,fox chase cancer center,philadelphia,pa, United States, center for familial breast and ovarian cancer and center of integrated oncology,university of cologne,cologne, Germany, center for familial breast and ovarian cancer and center of integrated oncology,university of cologne,cologne, Germany, department of obstetrics and gynaecology,klinikum rechts der isar,technical university,munich, Germany, division of oncology,department of gynaecology and obstetrics,university hospital schleswig-holstein,kiel, Germany, department of obstetrics and gynecology,ulm university,ulm, Germany, institut für humangenetik,charité-universitätsmedizin berlin,berlin, Germany, institute of human genetics,university of heidelberg,heidelberg, Germany, division of molecular genetics,department of gynaecology and obstetrics,clinical center university of düsseldorf,düsseldorf, Germany, n. n. petrov institute of oncology,saint-petersburg, Russian Federation, unité mixte de génétique constitutionnelle des cancers fréquents,centre hospitalier universitaire de lyon,centre léon bérard,lyon, France, equipe labellisée ligue 2008,umr5201 cnrs,centre léon bérard,université de lyon,lyon, France, inserm u509,service de génétique oncologique,institut curie,université paris-descartes,paris, France, equipe labellisée ligue 2008,umr5201 cnrs,centre léon bérard,université de lyon,lyon, France, equipe labellisée ligue 2008,umr5201 cnrs,centre léon bérard,université de lyon,lyon, France, inserm u509,service de génétique oncologique,institut curie,université paris-descartes,paris, France, inserm u509,service de génétique oncologique,institut curie,université paris-descartes,paris, France, département d'oncogénétique,centre jean perrin,université de clermont-ferrand,clermont-ferrand, France, département d'oncogénétique,centre jean 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laboratory,berkeley,ca,united states,center for cancer systems biology (ccsb) and department of cancer biology,dana-farber cancer institute,and department of genetics,harvard medical school,boston,ma, United States, department of internal medicine,epidemiology,human genetics,university of michigan,ann arbor,mi, United States, genetic counseling and hereditary cancer programme,catalan institute of oncology,idibell and girona biomedical research institute (idibgi),catalonia, Spain, genetic counseling and hereditary cancer programme,catalan institute of oncology,idibell and girona biomedical research institute (idibgi),catalonia, Spain, centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, abramson cancer center,university of pennsylvania school of medicine,philadelphia,pa,united states,centre for cancer genetic epidemiology,department of public health and primary care,university of cambridge,cambridge, United Kingdom, queensland institute of medical research,brisbane, Australia, department of obstetrics and gynaecologie,heinrich-heine-university,duesseldorf, Germany, biomedical research centre network for epidemiology and public health,spain,biomarkers and susceptibility unit,catalan institute of oncology,idibell,l'hospitalet,catalonia, Spain, translational research laboratory,catalan institute of oncology,bellvitge biomedical research institute (idibell),l'hospitalet,catalonia,spain,biomedical research centre network for epidemiology and public health,spain,biomarkers and susceptibility unit,catalan institute of oncology,idibell,l'hospitalet,catalonia, Spain



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