DNA damage induces alternative lengthening of telomeres (ALT) associated promyelocytic leukemia bodies that preferentially associate with linear telomeric DNA.

Abstract:

:The linear chromosomes of vertebrates terminate in telomeres that consist of a tandemly repeated hexameric sequence, 5'TTAGGG3'. Telomeres form a protective loop structure (t-loop), which is thought to prevent them from being recognized as a double-strand break. Approximately 10% of human tumors prevent shortening of their telomeres by using a recombination-mediated alternative lengthening of telomeres (ALT) mechanism. ALT-positive human cells contain extrachromosomal telomere repeat (ECTR) DNA that may either be circular or linear. It has been proposed that ECTR may be generated by recombination events involving the t-loop. A proportion of the cells within ALT-positive cell populations contain promyelocytic leukemia (PML) nuclear bodies that contain telomeric DNA and telomere-binding proteins that are called ALT-associated PML bodies (APB). Although the presence of APBs is very useful for determining whether tumors and cell lines use the ALT mechanism, the function of APBs is unknown. It has previously been shown that telomeric DNA is particularly susceptible to damage by hydrogen peroxide and N-methyl-N'-nitro-N-nitrosoguanidine. We report here that these DNA-damaging agents induce both linear and circular ECTR DNA in ALT cells and increase the proportion of cells that contain APBs. We partially purified APBs and showed that the telomeric repeat DNA they contain is predominantly linear. We propose that a function of APBs is to sequester linear telomeric DNA.

journal_name

Cancer Res

journal_title

Cancer research

authors

Fasching CL,Neumann AA,Muntoni A,Yeager TR,Reddel RR

doi

10.1158/0008-5472.CAN-07-1556

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

7072-7

issue

15

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-07-1556

journal_volume

67

pub_type

杂志文章
  • Mimicry of bryostatin 1 induced phosphorylation patterns in HL-60 cells by high-phorbol ester concentrations.

    abstract::The bryostatins are a group of macrocyclic lactones isolated from the marine bryozoan Bugula neritina. Bryostatin 1, like the phorbol esters, activates protein kinase C; however, it partially inhibits the phorbol ester induced differentiation of the human promyelocytic leukemic cell line HL-60. We compared the phospho...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Warren BS,Kamano Y,Pettit GR,Blumberg PM

    更新日期:1988-11-01 00:00:00

  • The CpG island methylator phenotype is not associated with a personal or family history of cancer.

    abstract::Colorectal cancers with widespread CpG island methylation display a number of distinct clinicopathological features, and it has been suggested that the condition has an inheritable genetic component. To address this possibility, histories of cancer were obtained from 562 individuals undergoing curative surgery for uns...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-03-3978

    authors: Ward RL,Williams R,Law M,Hawkins NJ

    更新日期:2004-10-15 00:00:00

  • High levels of tyrosine phosphorylated proto-ret in sporadic phenochromocytomas.

    abstract::Pheochromocytomas are tumors originating from chromaffin cells, the large majority of which are sporadic neoplasms. The genetic and molecular events determining their tumorigenesis continue to remain unknown. On the other hand, RET germ-line mutations cause the inheritance of familial tumors in multiple endocrine neop...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Le Hir H,Colucci-D'Amato LG,Charlet-Berguerand N,Plouin PF,Bertagna X,de Franciscis V,Thermes C

    更新日期:2000-03-01 00:00:00

  • The Raf inhibitor BAY 43-9006 (Sorafenib) induces caspase-independent apoptosis in melanoma cells.

    abstract::Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-i...

    journal_title:Cancer research

    pub_type: 杂志文章,收录出版

    doi:10.1158/0008-5472.CAN-05-0808

    authors: Panka DJ,Wang W,Atkins MB,Mier JW

    更新日期:2006-02-01 00:00:00

  • DNA amplification and tumorigenicity of the human melanoma cell line MeWo.

    abstract::Homogeneously staining regions (HSRs) were found in hypodiploid cells (40%) of a subline of the human melanoma cell line, MeWo, (MeWo-C) but were absent from the hypotetraploid cells (60%). Another subline (MeWo-B) was also shown to contain two populations of cells, 70% hypodiploid and 30% hypotetraploid. None of the ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Shtromas I,White BN,Holden JJ,Reimer DL,Roder JC

    更新日期:1985-02-01 00:00:00

  • Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer.

    abstract::Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-3373

    authors: Moughon DL,He H,Schokrpur S,Jiang ZK,Yaqoob M,David J,Lin C,Iruela-Arispe ML,Dorigo O,Wu L

    更新日期:2015-11-15 00:00:00

  • Expression profiling identifies altered expression of genes that contribute to the inhibition of transforming growth factor-beta signaling in ovarian cancer.

    abstract::Ovarian cancer is resistant to the antiproliferative effects of transforming growth factor-beta (TGF-beta); however, the mechanism of this resistance remains unclear. We used oligonucleotide arrays to profile 37 undissected, 68 microdissected advanced-stage, and 14 microdissected early-stage papillary serous cancers t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0683

    authors: Sunde JS,Donninger H,Wu K,Johnson ME,Pestell RG,Rose GS,Mok SC,Brady J,Bonome T,Birrer MJ

    更新日期:2006-09-01 00:00:00

  • Thrombospondin-1 type 1 repeat recombinant proteins inhibit tumor growth through transforming growth factor-beta-dependent and -independent mechanisms.

    abstract::Thrombospondin-1 (TSP-1) is a potent inhibitor of tumor growth and angiogenesis. The antiangiogenic activity of TSP-1 has been mapped to the procollagen homology region and the type 1 repeats (TSR) using synthetic peptides. To elucidate the molecular mechanisms that are involved in the inhibition of tumor growth by th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Miao WM,Seng WL,Duquette M,Lawler P,Laus C,Lawler J

    更新日期:2001-11-01 00:00:00

  • Ablation of the Brca1-Palb2 Interaction Phenocopies Fanconi Anemia in Mice.

    abstract::Heterozygous mutations in the BRCA1 gene predispose women to breast and ovarian cancer, while biallelic BRCA1 mutations are a cause of Fanconi anemia (FA), a rare genetic disorder characterized by developmental abnormalities, early-onset bone marrow failure, increased risk of cancers, and hypersensitivity to DNA-cross...

    journal_title:Cancer research

    pub_type: 评论,杂志文章

    doi:10.1158/0008-5472.CAN-20-0486

    authors: Park D,Bergin SM,Jones D,Ru P,Koivisto CS,Jeon YJ,Sizemore GM,Kladney RD,Hadjis A,Shakya R,Ludwig T

    更新日期:2020-10-01 00:00:00

  • Proliferation of human neuroblastomas mediated by the epidermal growth factor receptor.

    abstract::Neuroblastoma is a common solid tumor of childhood that is derived from the neural crest. Expression of epidermal growth factor (EGF) receptors (EGFRs) has been associated with enhanced cell growth and aggressive behavior in other tumors. Here, we examined the expression profile of EGFRs in neuroblastoma cell lines an...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-2426

    authors: Ho R,Minturn JE,Hishiki T,Zhao H,Wang Q,Cnaan A,Maris J,Evans AE,Brodeur GM

    更新日期:2005-11-01 00:00:00

  • Born to be exported: COOH-terminal nuclear export signals of different strength ensure cytoplasmic accumulation of nucleophosmin leukemic mutants.

    abstract::Creation of a nuclear export signal (NES) motif and loss of tryptophans (W) 288 and 290 (or 290 only) at the COOH terminus of nucleophosmin (NPM) are both crucial for NPM aberrant cytoplasmic accumulation in acute myelogenous leukemia (AML) carrying NPM1 mutations. Hereby, we clarify how these COOH-terminal alteration...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0273

    authors: Bolli N,Nicoletti I,De Marco MF,Bigerna B,Pucciarini A,Mannucci R,Martelli MP,Liso A,Mecucci C,Fabbiano F,Martelli MF,Henderson BR,Falini B

    更新日期:2007-07-01 00:00:00

  • Role for stromal heterogeneity in prostate tumorigenesis.

    abstract::Prostate cancer develops through a stochastic mechanism whereby precancerous lesions on occasion progress to multifocal adenocarcinoma. Analysis of human benign and cancer prostate tissues revealed heterogeneous loss of TGF-β signaling in the cancer-associated stromal fibroblastic cell compartment. To test the hypothe...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2999

    authors: Kiskowski MA,Jackson RS 2nd,Banerjee J,Li X,Kang M,Iturregui JM,Franco OE,Hayward SW,Bhowmick NA

    更新日期:2011-05-15 00:00:00

  • Thanatop: a novel 5-nitrofuran that is a highly active, cell-permeable inhibitor of topoisomerase II.

    abstract::A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-0393

    authors: Polycarpou-Schwarz M,Müller K,Denger S,Riddell A,Lewis J,Gannon F,Reid G

    更新日期:2007-05-01 00:00:00

  • Elements related to heterogeneity of antibody-dependent cell cytotoxicity in patients under trastuzumab therapy for primary operable breast cancer overexpressing Her2.

    abstract::Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis ...

    journal_title:Cancer research

    pub_type: 临床试验,杂志文章

    doi:10.1158/0008-5472.CAN-07-2068

    authors: Varchetta S,Gibelli N,Oliviero B,Nardini E,Gennari R,Gatti G,Silva LS,Villani L,Tagliabue E,Ménard S,Costa A,Fagnoni FF

    更新日期:2007-12-15 00:00:00

  • Lymphatic obstruction in carcinomatous ascites.

    abstract::The i.p. inoculation of C3H mice with 5 times 10-6 cells of a transplantable ovarian carcinoma invariably evokes accumulation of large amounts of ascitic fluid. Histological and pharmacotherapeutic studies indicate that obstruction to peritoneal lymphatic drainage is a key factor in the formation of carcinomatous asci...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Feldman GB

    更新日期:1975-02-01 00:00:00

  • Restricted T-cell receptor repertoire in melanoma metastases regressing after cytokine therapy.

    abstract::One major rationale for using interleukin-2 and IFN-alpha in cancer immunotherapy is to activate tumor-specific T cells at the tumor site. To study the in situ T-cell response, we determined the T-cell receptor (TCR) repertoire in six melanoma metastases regressing after cytokine treatment obtained from five patients....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Willhauck M,Scheibenbogen C,Pawlita M,Möhler T,Thiel E,Keilholz U

    更新日期:2003-07-01 00:00:00

  • Gonadotropins activate proteolysis and increase invasion through protein kinase A and phosphatidylinositol 3-kinase pathways in human epithelial ovarian cancer cells.

    abstract::Despite evidence that gonadotropins may facilitate peritoneal metastasis of ovarian cancer by increasing cell adhesion, the action and molecular mechanism of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ovarian cancer invasion is not well characterized. In the present study, we investigated the e...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-1785

    authors: Choi JH,Choi KC,Auersperg N,Leung PC

    更新日期:2006-04-01 00:00:00

  • Adoptive transfer enables tumor rejection targeted against a self-antigen without the induction of autoimmunity.

    abstract::We have previously described a tumor model in which the influenza hemagglutinin protein (HA) expressed on the BALB/c-derived MT901 tumor line serves as an immunization-dependent tumor rejection antigen in normal syngeneic mice. Although the HA antigen in this model is clearly foreign to normal BALB/c mice, many tumor ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Eck SC,Turka LA

    更新日期:2001-04-01 00:00:00

  • miRNA-708 control of CD44(+) prostate cancer-initiating cells.

    abstract::Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumor-initiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44(+) subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-0540

    authors: Saini S,Majid S,Shahryari V,Arora S,Yamamura S,Chang I,Zaman MS,Deng G,Tanaka Y,Dahiya R

    更新日期:2012-07-15 00:00:00

  • Genetic differences in metabolism of benzo(a)pyrene in cultured epidermal and dermal cells of responsive and nonresponsive mice.

    abstract::Genetic differences in metabolism of benzo(a)pyrene (BP) were investigated using cultured epidermal keratinocytes and dermal fibroblasts isolated from four inbred strains of mice: C3H/HeJms and C57BL/6J that are responsive; and DBA/2 and AKR/Jms that are nonresponsive in terms of inducibility of aryl hydrocarbon hydro...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hosomi J,Nemoto N,Kuroki T

    更新日期:1983-08-01 00:00:00

  • Phosphorylation and degradation of MdmX is inhibited by Wip1 phosphatase in the DNA damage response.

    abstract::MdmX and Mdm2 regulate p53 tumor suppressor functions by controlling p53 transcriptional activity and/or stability in cells exposed to DNA damage. Accumulating evidence indicates that ATM-mediated phosphorylation and degradation of Mdm2 and MdmX may be the initial driving force that induces p53 activity during the ear...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-0634

    authors: Zhang X,Lin L,Guo H,Yang J,Jones SN,Jochemsen A,Lu X

    更新日期:2009-10-15 00:00:00

  • The frequency of germ-line mutations in the breast cancer predisposition genes BRCA1 and BRCA2 in familial prostate cancer. The Cancer Research Campaign/British Prostate Group United Kingdom Familial Prostate Cancer Study Collaborators.

    abstract::Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectiv...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gayther SA,de Foy KA,Harrington P,Pharoah P,Dunsmuir WD,Edwards SM,Gillett C,Ardern-Jones A,Dearnaley DP,Easton DF,Ford D,Shearer RJ,Kirby RS,Dowe AL,Kelly J,Stratton MR,Ponder BA,Barnes D,Eeles RA

    更新日期:2000-08-15 00:00:00

  • Cooperation between v-fos and v-rasHA induces autonomous papillomas in transgenic epidermis but not malignant conversion.

    abstract::Transgenic mice have been previously established that express v-rasHa or v-fos exclusively in the epidermis by means of a targeting vector based on the human keratin 1 gene (HK1). Epidermal expression of v-rasHa (HK1.ras) or v-fos (HK1.fos) resulted in hyperplasia, hyperkeratosis, and later, in benign tumors. To asses...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Greenhalgh DA,Quintanilla MI,Orengo CC,Barber JL,Eckhardt JN,Rothnagel JA,Roop DR

    更新日期:1993-11-01 00:00:00

  • Ectopic expression of P-cadherin correlates with promoter hypomethylation early in colorectal carcinogenesis and enhanced intestinal crypt fission in vivo.

    abstract::P-cadherin is normally expressed in the basal layer of squamous epithelia and absent from the healthy intestine and colon. We have previously shown it to be expressed in all inflamed, hyperplastic, and dysplastic intestinal and colonic mucosa. This study aimed to better understand the mechanisms controlling the expres...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-0020

    authors: Milicic A,Harrison LA,Goodlad RA,Hardy RG,Nicholson AM,Presz M,Sieber O,Santander S,Pringle JH,Mandir N,East P,Obszynska J,Sanders S,Piazuelo E,Shaw J,Harrison R,Tomlinson IP,McDonald SA,Wright NA,Jankowski JA

    更新日期:2008-10-01 00:00:00

  • Prognostic value and function of KLF4 in prostate cancer: RNAa and vector-mediated overexpression identify KLF4 as an inhibitor of tumor cell growth and migration.

    abstract::KLF4/GLKF4 is a transcription factor that can have divergent functions in different malignancies. The role of KLF4 in prostate cancer etiology remains unclear. We have recently reported that small double-stranded RNA can induce gene expression by targeting promoter sequence in a phenomenon referred to as RNA activatio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2414

    authors: Wang J,Place RF,Huang V,Wang X,Noonan EJ,Magyar CE,Huang J,Li LC

    更新日期:2010-12-15 00:00:00

  • Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide.

    abstract::Glioblastoma (GBM) is often treated with the cytotoxic drug temozolomide, but the disease inevitably recurs in a drug-resistant form after initial treatment. Here, we report that in GBM cells, even a modest decrease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sensitivity...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-3616

    authors: McFaline-Figueroa JL,Braun CJ,Stanciu M,Nagel ZD,Mazzucato P,Sangaraju D,Cerniauskas E,Barford K,Vargas A,Chen Y,Tretyakova N,Lees JA,Hemann MT,White FM,Samson LD

    更新日期:2015-08-01 00:00:00

  • Effect of triamcinolone acetonide on the growth of NEL-M1 human melanoma cells cultured in the presence and absence of growth stimulatory agents.

    abstract::The human melanoma cell line NEL-M1 proliferates in Ham's F-12 medium in the absence of serum, hormones, and growth factors. Culturing NEL-M1 cells in defined medium supplemented with insulin (5 micrograms/ml) and transferrin (5 micrograms/ml) results in a 94% increase in [3H]thymidine incorporation after 24 h and a 6...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: DiSorbo DM

    更新日期:1986-08-01 00:00:00

  • Abrogation of shedding of immunosuppressive neuroblastoma gangliosides.

    abstract::Shedding of tumor cell gangliosides may contribute to tumor cell escape from host immune destruction. Thus, it would be of interest to block the shedding of these immunosuppressive molecules. To this end, we studied a ceramide analogue, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP). D-PDMP is a pot...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Li R,Ladisch S

    更新日期:1996-10-15 00:00:00

  • p53 mutations in non-small cell lung cancer in Japan: association between mutations and smoking.

    abstract::The p53 gene has been implicated as a tumor suppressor gene involved in the pathogenesis of lung cancer. Our previous study revealed that the p53 gene is frequently mutated with a distinct nucleotide substitution pattern in small cell lung cancer specimens in Japanese patients. In this study, we examined 30 primary, r...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Suzuki H,Takahashi T,Kuroishi T,Suyama M,Ariyoshi Y,Takahashi T,Ueda R

    更新日期:1992-02-01 00:00:00

  • Acquisition of resistance to antifolates caused by enhanced gamma-glutamyl hydrolase activity.

    abstract::A subline of H35 hepatoma cells has been developed which exhibits 80-fold resistance to 5,10-dideazatetrahydrofolate, an antifolate which inhibits glycinamideribonucleotide transformylase. The cells are cross-resistant to methotrexate, an inhibitor of dihydrofolate reductase and 10-propargyl-5,8-dideazafolate and its ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Rhee MS,Wang Y,Nair MG,Galivan J

    更新日期:1993-05-15 00:00:00