中国公众合理用药援助系统
药品查询
请勾选查询条件后检索
药品名 企业名 批准文号 功能主治
你的位置:首页 > 药讯频道 > 药讯 > 学术科研 > 正文
乳腺干细胞研究进展
www.yongyao.net  2009-1-12 13:51:34  来源:  责任编辑:
分享到:

5 乳腺干细胞应用前景

乳腺干细胞研究将极大地推进对乳腺发育、乳腺癌形成的了解以及乳腺癌治疗方法的发展。目前的资料表明,少量的癌症干细胞就可发展为乳腺癌,提示应重新评估目前治疗乳腺癌的方法。我们治疗乳腺癌患者的大多数方法是针对增殖和终末分化的细胞,这些疗法可能会暂时导致肿瘤萎缩,但不能清除肿瘤干细胞。而肿瘤干细胞可能会抵抗放疗和化疗,增加肿复发风险。因此,研究乳腺干细胞和乳腺癌干细胞是建立更好治疗方法的关键。

参考文献:

[ 1 ] Robinson GW. Cooperation of signalling pathways in embryonic mam2mary gland development[ J ]. Nat Rev Genet, 2007, 8 (12) : 963 - 972.

[ 2 ] Watson C J, KhaledW T. Mammary development in the embryo and a2dult: a journey of morphogenesis and commitment[ J ]. Development,2008, 135 (6) : 995 - 1003.

[ 3 ] SmalleyM, Ashworth A. Stem cells and breast cancer: A field in tran2sit[ J ]. Nat Rev Cancer, 2003, 3 (11) : 832 - 844.

[ 4 ] Deome K B, Faulkin L J, J r. , Bern H A, et al. Development ofmammary tumors from hyperp lastic alveolar nodules transp lanted intogland - free mammary fat pads of female C3H mice [ J ]. Cancer Res,1959, 19 (5) : 515 - 520.

[ 5 ] Smith G H, Medina D. A morphologically distinct candidate for an ep i2thelial stem cell in mouse mammary gland [ J ]. J Cell Sci, 1988, 90( Pt 1) : 173 - 183.

[ 6 ] ShackletonM, Vaillant F, Simp son K J, et al. Generation of a func2tionalmammary gland from a single stem cell[ J ]. Nature, 2006, 439(7072) : 84 - 88.

[ 7 ] Visvader J E, Lindeman G J. Mammary stem cells and mammopoiesis[ J ]. Cancer Res, 2006, 66 (20) : 9798 - 9801.

[ 8 ] Jones P H, Harper S, Watt FM. Stem cell patterning and fate in hu2man ep idermis[ J ]. Cell, 1995, 80 (1) : 83 - 93.

[ 9 ] Rietze R L, Valcanis H, Brooker G F, et al. Purification of a p luripo2tent neural stem cell from the adult mouse brain [ J ]. Nature, 2001,412 (6848) : 736 - 739.

[ 10 ] Dontu G, AbdallahW M, Foley J M, et al. In vitro p ropagation andtranscrip tional p rofiling of human mammary stem /p rogenitor cells[ J ].GenesDev, 2003, 17 (10) : 1253 - 1270.

[ 11 ] Brennan K R, Brown A M. Wnt proteins in mammary development andcancer[ J ]. JMammary Gland BiolNeoplasia, 2004, 9 (2) : 119 - 131.

[ 12 ] Brisken C, Heineman A, Chavarria T, et al. Essential function ofWnt24 inmammary gland development downstream of p rogesterone sig2naling[ J ]. GenesDev, 2000, 14 (6) : 650 - 654.

[ 13 ] Robinson GW, Hennighausen L, Johnson P F. Side2branching in themammary gland: the p rogesterone2Wnt connection [ J ]. Genes Dev,2000, 14 (8) : 889 - 894.

[ 14 ] Hsu W, Shakya R, Costantini F. Impaired mammary gland andlymphoid development caused by inducible exp ression of Axin intransgenic mice[ J ]. J Cell Biol, 2001, 155 (6) : 1055 - 1064.

[ 15 ] Wang X Y, Yin Y, Yuan H, et al. Musashi1 modulatesmammary pro2genitor cell expansion through p roliferin2mediated activation of theWntand Notch pathways[ J ]. Mol Cell Biol, 2008, 28 (11) : 3589 - 3599.

[ 16 ] Glenney J R, J r. , SoppetD. Sequence and exp ression of caveolin, ap rotein component of caveolae p lasmamembrane domains phosphoryla2ted on tyrosine in Rous sarcoma virus2transformed fibroblasts [ J ].Proc Natl Acad Sci U S A, 1992, 89 (21) : 10517 - 10521.

[ 17 ] Sotgia F, Williams T M, Cohen A W, et al. Caveolin212deficientmice have an increased mammary stem cell population with up regula2tion ofWnt/beta2catenin signaling[ J ]. Cell Cycle, 2005, 4 ( 12 ) :1808 - 1816.

[ 18 ] Okamoto T, SchlegelA, Scherer P E, et al. Caveolins, a family of scaf2folding proteins for organizing“preassembled signaling complexes”at theplasma membrane[ J ]. J Biol Chem, 1998, 273 (10) : 5419 - 5422.

[ 19 ] Cohen A W, Hnasko R, SchubertW, et al. Role of caveolae andcaveolins in health and disease [ J ]. Physiol Rev, 2004, 84 ( 4 ) :1341 - 1379.

[ 20 ] Scherer P E, Okamoto T, Chun M, et al. Identification, sequence,and exp ression of caveolin22 defines a caveolin gene family[ J ]. ProcNatl Acad Sci U S A, 1996, 93 (1) : 131 - 135.

[ 21 ] Li Y, Welm B, Podsypanina K, et al. Evidence that transgenes enco2ding components of the Wnt signaling pathway p referentially inducemammary cancers from p rogenitor cells[ J ]. Proc Natl Acad Sci U SA, 2003, 100 (26) : 15853 - 15858.

[ 22 ] Galbiati F, Volonte D, Brown A M, et al. Caveolin21 exp ression in2hibitsWnt /beta2catenin /Lef21 signaling by recruiting beta2catenin tocaveolae membrane domains [ J ]. J Biol Chem, 2000, 275 ( 30 ) :23368 - 23377.

[ 23 ] Bradley R S, Brown A M. A soluble form ofWnt21 p rotein with mito2genic activity on mammary ep ithelial cells[ J ]. Mol Cell Biol, 1995,15 (8) : 4616 - 4622.

[ 24 ] Liu B Y, McDermott S P, Khwaja S S, et al. The transforming activi2ty ofWnt effectors correlateswith their ability to induce the accumula2tion of mammary p rogenitor cells [ J ]. Proc Natl Acad Sci U S A,2004, 101 (12) : 4158 - 4163.

[ 25 ] EblaghieM C, Song S J, Kim J Y, et al. Interactions between FGFandWnt signals and Tbx3 gene exp ression in mammary gland initia2tion in mouse embryos[ J ]. J Anat, 2004, 205 (1) : 1 - 13.

[ 26 ] Dillon C, Spencer2Dene B, Dickson C. A crucial role for fibroblastgrowth factor signaling in embryonicmammary gland development[ J ].J Mammary Gland Biol Neop lasia, 2004, 9 (2) : 207 - 215.

[ 27 ] Peters G, Brookes S, Smith R, et al. Tumorigenesis bymouse mam2mary tumor virus: evidence for a common region for p rovirus integra2tion in mammary tumors[ J ]. Cell, 1983, 33 (2) : 369 - 377.

[ 28 ] MullerW J, Lee F S, Dickson C, et al. The int22 gene p roduct actsas an ep ithelial growth factor in transgenic mice[ J ]. EMBO J, 1990,9 (3) : 907 - 913.

[ 29 ] Stamp G, Fantl V, Poulsom R, et al. Nonuniform exp ression of amouse mammary tumor virus2driven int22 /Fgf23 transgene in p regnan2cy2responsive breast tumors[ J ]. Cell Growth Differ , 1992, 3 ( 12) :929 - 938.

[ 30 ] Ornitz D M, Moreadith R W, Leder P. Binary system for regulatingtransgene exp ression in mice: targeting int22 gene exp ression withyeast GAL4 /UAS control elements[ J ]. Proc Natl Acad Sci U S A,1991, 88 (3) : 698 - 702.

[ 31 ] Smith G H, Chepko G. Mammary ep ithelial stem cells[ J ]. MicroscRes Tech, 2001, 52 (2) : 190 - 203.

[ 32 ] Gallahan D, Callahan R. The mouse mammary tumor associated geneINT3 is a unique member of the NOTCH gene family (NOTCH4 )[ J ]. Oncogene, 1997, 14 (16) : 1883 - 1890.

[ 33 ] Callahan R, Egan S E. Notch signaling in mammary development andoncogenesis[ J ]. J Mammary Gland Biol Neop lasia, 2004, 9 ( 2 ) :145 - 163.

[ 34 ] Dontu G, Jackson KW, McNicholas E, et al. Role ofNotch signalingin cell2fate determination of human mammary stem /p rogenitor cells[ J ]. Breast Cancer Res, 2004, 6 (6) : R605 - R615.

[ 35 ] Axelson H, Fredlund E, OvenbergerM, et al. Hypoxia2induced ded2ifferentiation of tumor cellsa mechanism behind heterogeneity andaggressiveness of solid tumors[ J ]. Semin CellDev Biol, 2005, 16 (4- 5) : 554 - 563.

[ 36 ] GustafssonM V, Zheng X, Pereira T, et al. Hypoxia requires notchsignaling to maintain the undifferentiated cell state [ J ]. Dev Cell,2005, 9 (5) : 617 - 628.

[ 37 ] Sansone P, Storci G, Giovannini C, et al. p66Shc /Notch23 interp laycontrolsself2renewal and hypoxia survival in human stem /p rogenitorcells of the mammary gland expanded in vitro as mammospheres[ J ].Stem Cells, 2007, 25 (3) : 807 - 815.

[ 38 ] Suda T, Arai F, Hirao A. Hematopoietic stem cells and their niche[ J ]. Trends Immunol, 2005, 26 (8) : 426 - 433.

[ 39 ] Li N, Singh S, Cherukuri P, et al. Recip rocal intraep ithelial interac2tions between TP63 and hedgehog signaling regulate quiescence andactivation of p rogenitor elaboration by mammary stem cells[ J ]. StemCells, 2008, 26 (5) : 1253 - 1264.

[ 40 ] LewisM T, Ross S, Strickland P A, et al. Defects in mousemamma2ry gland development caused by conditional hap loinsufficiency ofPatched21 [ J ]. Development, 1999, 126 (22) : 5181 - 5193.

[ 41 ] LewisM T, Ross S, Strickland P A, et al. The Gli2 transcrip tion fac2tor is required for normal mouse mammary gland development [ J ].Dev Biol, 2001, 238 (1) : 133 - 144.

[ 42 ] Liu S, Dontu G, Mantle ID, et al. Hedgehog signaling and Bmi21regulate self2renewal of normal and malignant human mammary stemcells[ J ]. Cancer Res, 2006, 66 (12) : 6063 - 6071.

[ 43 ] Machold R, Hayashi S, RutlinM, et al. Sonic hedgehog is requiredfor p rogenitor cellmaintenance in telencephalic stem cell niches[ J ].Neuron, 2003, 39 (6) : 937 - 950.

[ 44 ] LewisM T, Visbal A P. The hedgehog signaling network, mammarystem cells, and breast cancer: connections and controversies [ J ].Ernst Schering Found Symp Proc, 2006, (5) : 181 - 217.

[ 45 ] Moraes R C, Zhang X, Harrington N, et al. Constitutive activation ofsmoothened ( SMO) in mammary glands of transgenic mice leads toincreased p roliferation, altered differentiation and ductal dysp lasia[ J ]. Development, 2007, 134 (6) : 1231 - 1242.

[ 46 ] BamshadM, Lin R C, Law D J, et al. Mutations in human TBX3 al2ter limb, apocrine and genital development in ulnar2mammary syn2drome[ J ]. Nat Genet, 1997, 16 (3) :311 - 315.

[ 47 ] BamshadM, Le T, WatkinsW S, et al. The spectrum ofmutations inTBX3: Genotype /Phenotype relationship in ulnar2mammary syndrome[ J ]. Am J Hum Genet, 1999, 64 (6) : 1550 - 1562.

[ 48 ] Jerome2Majewska L A, Jenkins G P, et al. Tbx3, the ulnar2mammarysyndrome gene, and Tbx2 interact in mammary gland developmentthrough a p19Arf /p532independent pathway [ J ]. Dev Dyn, 2005,234 (4) : 922 - 933.

[ 49 ] Davenport T G, Jerome2Majewska L A, Papaioannou V E. Mammarygland, limb and yolk sac defects in mice lacking Tbx3, the gene mu2tated in human ulnar mammary syndrome [ J ]. Development, 2003,130 (10) : 2263 - 2273.

[ 50 ] FanW, Huang X, Chen C, et al. TBX3 and its isoform TBX3 + 2aare functionally distinctive in inhibition of senescence and are overex2p ressed in a subset of breast cancer cell lines[ J ]. Cancer Res, 2004,64 (15) : 5132 - 5139.

[ 51 ] LomnytskaM, Dubrovska A, Hellman U, et al. Increased exp ressionof cSHMT, Tbx3 and utrophin in p lasma of ovarian and breast cancerpatients[ J ]. Int J Cancer, 2006, 118 (2) : 412 - 421.

[ 52 ] YaroshW, Barrientos T, Esmailpour T, et al. TBX3 is overexp ressedin breast cancer and rep resses p14ARF by interacting with histonedeacetylases[ J ]. Cancer Res, 2008, 68 (3) : 693 - 699.

[ 53 ] Carlson H, Ota S, Campbell C E, et al. A dominant rep ression do2main in Tbx3 mediates transcrip tional rep ression and cell immortaliza2tion: relevance to mutations in Tbx3 that cause ulnar2mammary syn2drome[ J ]. Hum Mol Genet, 2001, 10 (21) : 2403 - 2413.

[ 54 ] Carlson H, Ota S, Song Y, et al. Tbx3 imp inges on the p53 pathwayto supp ress apop tosis, facilitate cell transformation and block myogen2ic differentiation[ J ]. Oncogene, 2002, 21 (24) : 3827 - 3835.

[ 55 ] Brummelkamp T R, Kortlever R M, LingbeekM, et al. TBX23, thegene mutated in Ulnar2Mammary Syndrome, is a negative regulator ofp19ARF and inhibits senescence[ J ]. J Biol Chem, 2002, 277 ( 8) :6567 - 6572.

[ 56 ] Ito A, AsamotoM, HokaiwadoN, et al. Tbx3 expression is related to ap2optosis and cell proliferation in rat bladder both hyperplastic epithelialcells and carcinoma cells[ J ]. Cancer Lett, 2005, 219 (1) : 105 - 112.

[ 57 ] Renard C A, Labalette C, Armengol C, et al. Tbx3 is a downstreamtarget of theWnt/ beta2catenin pathway and a criticalmediator of beta2catenin survival functions in liver cancer[ J ]. Cancer Res, 2007, 67(3) : 901 - 910.

[ 58 ] Chu E Y, Hens J, Andl T, et al. CanonicalWNT signaling p romotesmammary p lacode development and is essential for initiation of mam2mary gland morphogenesis[ J ]. Development, 2004, 131 (19) : 4819- 4829.

[ 59 ] Kouros2Mehr H, Slorach EM, SternlichtM D, et al. GATA23 main2tains the differentiation of the luminal cell fate in the mammary gland[ J ]. Cell, 2006, 127 (5) : 1041 - 1055.

[ 60 ] WrightM H, Calcagno AM, Salcido C D, et al. Brca1 breast tumorscontain distinct CD44 + /CD24 - and CD133 + cells with cancer stemcell characteristics[ J ]. Breast Cancer Res, 2008, 10 (1) : R10.

[ 61 ] Zucchi I, Sanzone S, Astigiano S, et al. The p roperties of amammarygland cancer stem cell[ J ]. Proc Natl Acad Sci U S A, 2007, 104(25) : 10476 - 10481.

[ 62 ] Chute J P, Muramoto G G, Whitesides J, et al. Inhibition of alde2hyde dehydrogenase and retinoid signaling induces the expansion ofhuman hematopoietic stem cells [ J ]. Proc Natl Acad Sci U S A,2006, 103 (31) : 11707 - 11712.

[ 63 ] HessD A, Wirthlin L, Craft T P, et al. Selection based on CD133and high aldehyde dehydrogenase activity isolates long2term reconstitu2ting human hematopoietic stem cells [ J ]. Blood, 2006, 107 ( 5 ) :2162 - 2169.

[ 64 ] Christ O, Lucke K, Imren S, et al. Imp roved purification of hemato2poietic stem cells based on their elevated aldehyde dehydrogenase ac2tivity[ J ]. Haematologica, 2007, 92 (9) : 1165 - 1172.

[ 65 ] Pearce D J, Bonnet D. The combined use of Hoechst efflux ability andaldehyde dehydrogenase activity to identifymurine and human hematopoi2etic stem cells[ J ]. Exp Hematol, 2007, 35 (9) : 1437 - 1446.

[ 66 ] Povsic T J, Zavodni K L, Kelly F L, et al. Circulating p rogenitorcells can be reliably identified on the basis of aldehyde dehydrogenaseactivity[ J ]. J Am Coll Cardiol, 2007, 50 (23) : 2243 - 2248.

[ 67 ] Ginestier C, HurM H, Charafe2Jauffret E, et al. ALDH1 is a marker ofnormal and malignant human mammary stem cells and a predictor of poorclinical outcome[ J ]. Cell Stem Cell, 2007, 1 (5) : 555 - 567.

[ 68 ] Villadsen R, FridriksdottirA J, Ronnov2Jessen L, et al. Evidence fora stem cell hierarchy in the adult human breast [ J ]. J Cell Biol,2007, 177 (1) : 87 - 101.

[ 69 ] Shafee N, Smith C R, Wei S, et al. Cancer stem cells contribute tocisp latin resistance in Brca1 /p532mediated mouse mammary tumors[ J ]. Cancer Res, 2008, 68 (9) : 3243 - 3250.

[ 70 ] Engelmann K, Shen H, Finn O J. MCF7 side population cells withcharacteristics of cancer stem /p rogenitor cells exp ress the tumor anti2genMUC1 [ J ]. Cancer Res, 2008, 68 (7) : 2419 - 2426.

[ 71 ] Li Y, Kong L, Yang Y, et al. Mutant TNFalpha negatively regulateshuman breast cancer stem cells from MCF7 in vitro[ J ]. Cancer BiolTher, 2007, 6 (9) : 1480 - 1489.

[ 72 ] Li H Z, Yi TB, Wu Z Y. Suspension culture combined with chemo2therapeutic agents for sorting of breast cancer stem cells [ J ]. BMCCancer, 2008, 8: 135.

免责声明:本文仅代表作者个人观点,与本网无关。转载目的在于传递更多信息,并不代表本网赞同其观点和对其真实性负责。对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不作任何保证或承诺,请读者仅作参考,并请自行核实相关内容。
返回资讯中心 返回资讯列表