Organoid cultures derived from patients with advanced prostate cancer.


:The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circulating tumor cells. The first seven fully characterized organoid lines recapitulate the molecular diversity of prostate cancer subtypes, including TMPRSS2-ERG fusion, SPOP mutation, SPINK1 overexpression, and CHD1 loss. Whole-exome sequencing shows a low mutational burden, consistent with genomics studies, but with mutations in FOXA1 and PIK3R1, as well as in DNA repair and chromatin modifier pathways that have been reported in advanced disease. Loss of p53 and RB tumor suppressor pathway function are the most common feature shared across the organoid lines. The methodology described here should enable the generation of a large repertoire of patient-derived prostate cancer lines amenable to genetic and pharmacologic studies.






Gao D,Vela I,Sboner A,Iaquinta PJ,Karthaus WR,Gopalan A,Dowling C,Wanjala JN,Undvall EA,Arora VK,Wongvipat J,Kossai M,Ramazanoglu S,Barboza LP,Di W,Cao Z,Zhang QF,Sirota I,Ran L,MacDonald TY,Beltran H,Mosquera J




Has Abstract


2014-09-25 00:00:00
















  • Self-eating limits EGFR-dependent tumor growth.

    abstract::Autophagy is a cell-autonomous, catabolic process that plays context-dependent roles in tumor growth and progression. Wei et al. report that EGFR signaling promotes tumor growth through phosphorylation and functional inactivation of Beclin 1 and the consequent suppression of autophagy. ...


    pub_type: 评论,杂志文章


    authors: Fantin VR,Abraham RT

    更新日期:2013-09-12 00:00:00

  • At loose ends: resecting a double-strand break.

    abstract::Double-strand break (DSB) repair is critical for maintaining genomic integrity and requires the processing of the 5' DSB ends. Recent studies have shed light on the mechanism and regulation of DNA end processing during DSB repair by homologous recombination. ...


    pub_type: 杂志文章,评审


    authors: Bernstein KA,Rothstein R

    更新日期:2009-05-29 00:00:00

  • Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals.

    abstract::The sphingomyelin pathway, which is initiated by sphingomyelin hydrolysis to generate the second messenger ceramide, signals apoptosis for tumor necrosis factor alpha, Fas, and ionizing radiation. In the present studies, the anticancer drug daunorubicin also stimulated ceramide elevation and apoptosis in P388 and U937...


    pub_type: 杂志文章


    authors: Bose R,Verheij M,Haimovitz-Friedman A,Scotto K,Fuks Z,Kolesnick R

    更新日期:1995-08-11 00:00:00

  • Expression of the v-erbA oncogene in chicken embryo fibroblasts stimulates their proliferation in vitro and enhances tumor growth in vivo.

    abstract::In contrast to uninfected chicken embryo fibroblasts (CEFs), CEFs infected with a retroviral vector that carries the v-erbA gene of avian erythroblastosis virus displayed new properties. These included limited anchorage-independent growth in soft agar, growth without latency in serum-supplemented medium, ability to ov...


    pub_type: 杂志文章


    authors: Gandrillon O,Jurdic P,Benchaibi M,Xiao JH,Ghysdael J,Samarut J

    更新日期:1987-06-05 00:00:00

  • Methyl labeling of HeLa cell hnRNA: a comparison with mRNA.

    abstract::The majority of the mRNA molecules in HeLa cells contain 1-2 residue(s) of m6Ap and one blocked, methylated 5' terminal "cap" structure. The hnRNA, which is longer than mRNA, contains both m6Ap and caps but 4-6 times as many m6Ap residues per chain. In addition, nuclear molecules contain T2 RNA ase-resistant, methyl-l...


    pub_type: 杂志文章


    authors: Salditt-Georgieff M,Jelinek W,Darnell JE,Furuichi Y,Morgan M,Shatkin A

    更新日期:1976-02-01 00:00:00

  • Histone Acetylome-wide Association Study of Autism Spectrum Disorder.

    abstract::The association of histone modification changes with autism spectrum disorder (ASD) has not been systematically examined. We conducted a histone acetylome-wide association study (HAWAS) by performing H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq) on 257 postmortem samples from ASD and matched control brai...


    pub_type: 杂志文章


    authors: Sun W,Poschmann J,Cruz-Herrera Del Rosario R,Parikshak NN,Hajan HS,Kumar V,Ramasamy R,Belgard TG,Elanggovan B,Wong CCY,Mill J,Geschwind DH,Prabhakar S

    更新日期:2016-11-17 00:00:00

  • Growth-rate-dependent regulation of ribosome synthesis in E. coli: expression of the lacZ and galK genes fused to ribosomal promoters.

    abstract::Hybrid transducing phages were constructed in vitro that carry the galK gene fused to each of three ribosomal promoters: the promotor for an rRNA operon (rrnE); the promoter for the spec r protein operon and the promotor for the alpha r protein operon. We also constructed hybrid transducing phages that carry the IacZ ...


    pub_type: 杂志文章


    authors: Miura A,Krueger JH,Itoh S,de Boer HA,Nomura M

    更新日期:1981-09-01 00:00:00

  • The relationship between transformation and somatic mutation in human and Chinese hamster cells.

    abstract::The frequencies of transformations of primary human and Chinese hamster fibroblasts have been compared with the spontaneous and induced frequencies of mutation for resistance to thioguanine and ouabain, and for ability to use fructose, using the carcinogens benzo (alpha) pyrene and urethane. Whereas the rates and freq...


    pub_type: 杂志文章


    authors: Spandidos DA,Siminovitch L

    更新日期:1978-04-01 00:00:00

  • Nonpolarized expression of a secreted murine leukemia virus glycoprotein in polarized epithelial cells.

    abstract::Vaccinia virus recombinants were generated which express the intact gp70/p15E of Friend mink cell focus inducing virus (F-MCFV) or truncated forms of the glycoprotein that lack the transmembrane and cytoplasmic domains. The transport of the intact and truncated envelope glycoproteins to apical or basolateral surfaces ...


    pub_type: 杂志文章


    authors: Stephens EB,Compans RW

    更新日期:1986-12-26 00:00:00

  • A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube.

    abstract::Distinct classes of neurons are generated at defined positions in the ventral neural tube in response to a gradient of Sonic Hedgehog (Shh) activity. A set of homeodomain transcription factors expressed by neural progenitors act as intermediaries in Shh-dependent neural patterning. These homeodomain factors fall into ...


    pub_type: 杂志文章


    authors: Briscoe J,Pierani A,Jessell TM,Ericson J

    更新日期:2000-05-12 00:00:00

  • The inhibition by DRB (5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole) of hnRNA and mRNA production in HeLa cells.

    abstract::5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB; 75 muM) inhibited only 60-75% of nuclear heterogeneous RNA (hnRNA) synthesis in HeLa cells, while the appearance of labeled cytoplasmic poly(A)-containing messenger RNA (mRNA) was reduced by approximately 95%. DRB-sensitive and resistant transcripts spanned the e...


    pub_type: 杂志文章


    authors: Sehgal PB,Darnell JE Jr,Tamm I

    更新日期:1976-11-01 00:00:00

  • Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex.

    abstract::Drugs selectively targeting CB2 hold promise for treating neurodegenerative disorders, inflammation, and pain while avoiding psychotropic side effects mediated by CB1. The mechanisms underlying CB2 activation and signaling are poorly understood but critical for drug design. Here we report the cryo-EM structure of the ...


    pub_type: 杂志文章


    authors: Xing C,Zhuang Y,Xu TH,Feng Z,Zhou XE,Chen M,Wang L,Meng X,Xue Y,Wang J,Liu H,McGuire TF,Zhao G,Melcher K,Zhang C,Xu HE,Xie XQ

    更新日期:2020-02-20 00:00:00

  • Hexosamine pathway metabolites enhance protein quality control and prolong life.

    abstract::Aging entails a progressive decline in protein homeostasis, which often leads to age-related diseases. The endoplasmic reticulum (ER) is the site of protein synthesis and maturation for secreted and membrane proteins. Correct folding of ER proteins requires covalent attachment of N-linked glycan oligosaccharides. Here...


    pub_type: 杂志文章


    authors: Denzel MS,Storm NJ,Gutschmidt A,Baddi R,Hinze Y,Jarosch E,Sommer T,Hoppe T,Antebi A

    更新日期:2014-03-13 00:00:00

  • Compete globally, bud locally.

    abstract::How cells generate a single axis of polarity for mating, division, and movement is unknown. In this issue, Howell et al. (2009) use a synthetic biology approach to demonstrate that rapid competition for a soluble signaling component (Bem1) is essential to ensure a unique axis of polarity in budding yeast. ...


    pub_type: 评论,杂志文章


    authors: Houk AR,Millius A,Weiner OD

    更新日期:2009-11-13 00:00:00

  • A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B.

    abstract::Cyclin B is degraded at the onset of anaphase by a ubiquitin-dependent proteolytic system. We have fractionated mitotic Xenopus egg extracts to identify components required for this process. We find that UBC4 and at least one other ubiquitin-conjugating enzyme can support cyclin B ubiquitination. The mitotic specifici...


    pub_type: 杂志文章


    authors: King RW,Peters JM,Tugendreich S,Rolfe M,Hieter P,Kirschner MW

    更新日期:1995-04-21 00:00:00

  • Isolation and characterization of sigma(70)-retaining transcription elongation complexes from Escherichia coli.

    abstract::sigma(70) subunit is thought to be released from the core RNA polymerase (RNAP) upon the transition from initiation to elongation or shortly afterward. Here, we identify a population of RNAP from E. coli that retains sigma(70) throughout elongation. The relative amount of this population appears to depend on cellular ...


    pub_type: 杂志文章


    authors: Bar-Nahum G,Nudler E

    更新日期:2001-08-24 00:00:00

  • Antigen Identification for Orphan T Cell Receptors Expressed on Tumor-Infiltrating Lymphocytes.

    abstract::The immune system can mount T cell responses against tumors; however, the antigen specificities of tumor-infiltrating lymphocytes (TILs) are not well understood. We used yeast-display libraries of peptide-human leukocyte antigen (pHLA) to screen for antigens of "orphan" T cell receptors (TCRs) expressed on TILs from h...


    pub_type: 杂志文章


    authors: Gee MH,Han A,Lofgren SM,Beausang JF,Mendoza JL,Birnbaum ME,Bethune MT,Fischer S,Yang X,Gomez-Eerland R,Bingham DB,Sibener LV,Fernandes RA,Velasco A,Baltimore D,Schumacher TN,Khatri P,Quake SR,Davis MM,Garcia KC

    更新日期:2018-01-25 00:00:00

  • Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis.

    abstract::Dysfunction and loss of insulin-producing pancreatic beta cells represent hallmarks of diabetes mellitus. Here, we show that mice lacking the mitogen-activated protein kinase (MAPK) p38delta display improved glucose tolerance due to enhanced insulin secretion from pancreatic beta cells. Deletion of p38delta results in...


    pub_type: 杂志文章


    authors: Sumara G,Formentini I,Collins S,Sumara I,Windak R,Bodenmiller B,Ramracheya R,Caille D,Jiang H,Platt KA,Meda P,Aebersold R,Rorsman P,Ricci R

    更新日期:2009-01-23 00:00:00

  • Expression cloning of an activin receptor, a predicted transmembrane serine kinase.

    abstract::Activins are involved in the regulation of multiple biological events, ranging from early development to pituitary function. To characterize the cellular mechanisms involved in these processes, cDNAs coding for an activin receptor were cloned from AtT20 mouse corticotropic cells by screening COS cell transfectants for...


    pub_type: 杂志文章


    authors: Mathews LS,Vale WW

    更新日期:1991-06-14 00:00:00

  • Tumor promoter-induced changes in the permeability of epithelial cell tight junctions.

    abstract::Treatment of the kidney epithelial cell line MDCK with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) induces a large increase in the permeability of tight junctions within 2-4 hr. This change in transepithelial permeability is accompanied by alterations in cell morphology that include the opening of ti...


    pub_type: 杂志文章


    authors: Ojakian GK

    更新日期:1981-01-01 00:00:00

  • A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator.

    abstract::Regulated proteolysis is essential for cell cycle progression in both prokaryotes and eukaryotes. We show here that the ClpXP protease, responsible for the degradation of multiple bacterial proteins, is dynamically localized to specific cellular positions in Caulobacter where it degrades colocalized proteins. The CtrA...


    pub_type: 杂志文章


    authors: McGrath PT,Iniesta AA,Ryan KR,Shapiro L,McAdams HH

    更新日期:2006-02-10 00:00:00

  • The Rule of Three for Prizes in Science and the Bold Triptychs of Francis Bacon.

    abstract::For many scientific awards, such as Nobels and Laskers, the maximum number of recipients is three. This Rule of Three forces selection committees to make difficult decisions that increase the likelihood of singling out those individuals who open a new field and continue to lead it. The Rule of Three is reminiscent of ...


    pub_type: 杂志文章


    authors: Goldstein JL

    更新日期:2016-09-22 00:00:00

  • Biotech's perfect storm.

    abstract::The global financial crisis has hit biotech companies hard both in the US and Europe as venture capital dries up. Finding new sources of long-term financing for translating research into new therapeutics will be essential for maintaining innovation and new drug development by biotech companies. ...


    pub_type: 杂志文章


    authors: Karberg S

    更新日期:2009-08-07 00:00:00

  • A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry.

    abstract::Herpes simplex virus type 1 (HSV-1) binds to cells through interactions of viral glycoproteins gB and gC with heparan sulfate chains on cell surface proteoglycans. This binding is not sufficient for viral entry, which requires fusion between the viral envelope and cell membrane. Here, we show that heparan sulfate modi...


    pub_type: 杂志文章


    authors: Shukla D,Liu J,Blaiklock P,Shworak NW,Bai X,Esko JD,Cohen GH,Eisenberg RJ,Rosenberg RD,Spear PG

    更新日期:1999-10-01 00:00:00

  • Structure Studies of the CRISPR-Csm Complex Reveal Mechanism of Co-transcriptional Interference.

    abstract::Csm, a type III-A CRISPR-Cas interference complex, is a CRISPR RNA (crRNA)-guided RNase that also possesses target RNA-dependent DNase and cyclic oligoadenylate (cOA) synthetase activities. However, the structural features allowing target RNA-binding-dependent activation of DNA cleavage and cOA generation remain unkno...


    pub_type: 杂志文章


    authors: You L,Ma J,Wang J,Artamonova D,Wang M,Liu L,Xiang H,Severinov K,Zhang X,Wang Y

    更新日期:2019-01-10 00:00:00

  • Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs.

    abstract::Vertebrate Hoxd genes are sequentially activated during the morphogenesis and pattern formation of the limb. Using the approach of gene disruption via homologous recombination in embryonic stem cells, we have assessed the function of the last gene of the complex, Hoxd-13. Mutant mice displayed skeletal alterations alo...


    pub_type: 杂志文章


    authors: Dollé P,Dierich A,LeMeur M,Schimmang T,Schuhbaur B,Chambon P,Duboule D

    更新日期:1993-11-05 00:00:00

  • The interaction of recombination proteins with supercoiled DNA: defining the role of supercoiling in lambda integrative recombination.

    abstract::Lambda integrative recombination depends on supercoiling of the phage attachment site, attP. Using dimethylsulfate protection and indirect end-labeling, the interaction of the recombination proteins Int and IHF with supercoiled and linear attP has been studied. Supercoiling enhances the binding of Int to attP, but not...


    pub_type: 杂志文章


    authors: Richet E,Abcarian P,Nash HA

    更新日期:1986-09-26 00:00:00

  • Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia.

    abstract::Rho and rac, two members of the ras-related superfamily of small GTPases, regulate the polymerization of actin to produce stress fibers and lamellipodia, respectively. We report here that cdc42, another member of the rho family, triggers the formation of a third type of actin-based structure found at the cell peripher...


    pub_type: 杂志文章


    authors: Nobes CD,Hall A

    更新日期:1995-04-07 00:00:00

  • Structural basis for cargo regulation of COPII coat assembly.

    abstract::Using cryo-electron microscopy, we have solved the structure of an icosidodecahedral COPII coat involved in cargo export from the endoplasmic reticulum (ER) coassembled from purified cargo adaptor Sec23-24 and Sec13-31 lattice-forming complexes. The coat structure shows a tetrameric assembly of the Sec23-24 adaptor la...


    pub_type: 杂志文章


    authors: Stagg SM,LaPointe P,Razvi A,Gürkan C,Potter CS,Carragher B,Balch WE

    更新日期:2008-08-08 00:00:00

  • Connecting the dots between septins and the DNA damage checkpoint.

    abstract::In budding yeast, septins are involved in the morphogenesis checkpoint and the DNA damage checkpoint, both of which regulate cell-cycle progression. In this issue of Cell, Kremer et al. (2007) link septins to DNA damage in mammalian cells by identifying a new signaling pathway that includes the adaptors SOCS7 and NCK....


    pub_type: 评论,杂志文章


    authors: Kinoshita M,Takeda S

    更新日期:2007-09-07 00:00:00