Frequent hypermethylation of the RASSF1A gene in prostate cancer.

Abstract:

:Recently, we have cloned and characterized the Ras association domain family 1A gene (RASSF1A) at 3p21.3, from which loss of genetic material is one of the most frequent events in several types of human solid tumors. The CpG island promoter region of this gene is highly methylated in several human cancers, most notably in small cell lung cancer, breast cancer, and renal cell carcinoma. In this study, we have analysed the methylation status of RASSF1A in primary prostate tumors and in the prostate cancer cell line LNCaP. In total, 37 out of 52 tumors (71%) were methylated at the promoter region of RASSF1A. The relative frequency of methylation was higher in more aggressive tumors compared with less malignant tumors. For instance, tumors with a Gleason score of 7-10 (25 out of 30, 83%) were significantly more methylated compared with Gleason 4-6 tumors (11 out of 20, 55%, P=0.032, Fisher's exact test). Coincident with a hypermethylated promoter, transcripts of RASSF1A were missing in LNCaP cells. Expression of RASSF1A was restored with 5-aza-2'-deoxycytidine, a DNA methylation inhibitor. In conclusion, our data suggest that epigenetic inactivation of RASSF1A by methylation is a very common event in prostate cancer and might be involved in the progression of the disease. Testing for RASSF1A methylation should become useful in prostate cancer early detection and diagnosis and might aid prognosis by gauging the potential status of progression.

journal_name

Oncogene

journal_title

Oncogene

authors

Liu L,Yoon JH,Dammann R,Pfeifer GP

doi

10.1038/sj.onc.1205814

subject

Has Abstract

pub_date

2002-10-03 00:00:00

pages

6835-40

issue

44

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Expression of human immunodeficiency virus type I tat results in down-regulation of bcl-2 and induction of apoptosis in hematopoietic cells.

    abstract::Infection by human immunodeficiency virus type 1 (HIV-1) is characterized by progressive loss of various cell types, mainly CD4+ T lymphocytes. While a passive role for the virus in cell destruction is recognized, it does not account for the vast amount of cell death including those of uninfected "bystander' cells. Si...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Sastry KJ,Marin MC,Nehete PN,McConnell K,el-Naggar AK,McDonnell TJ

    更新日期:1996-08-01 00:00:00

  • HGF-independent potentiation of EGFR action by c-Met.

    abstract::The c-Met receptor is a potential therapeutic target for non-small cell lung cancer (NSCLC). Signaling interactions between c-Met and the mutant epidermal growth factor receptor (EGFR) have been studied extensively, but signaling intermediates and biological consequences of lateral signaling to c-Met in EGFR wild-type...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.84

    authors: Dulak AM,Gubish CT,Stabile LP,Henry C,Siegfried JM

    更新日期:2011-08-18 00:00:00

  • Tumour regression in a ligand inducible manner mediated by a chimeric tumour suppressor derived from p53.

    abstract::The p53 tumour suppressor induces cell cycle arrest and apoptosis in response to cellular stresses. p53 is inactivated by various cellular and viral factors. We set out to generate regulatable p53 derivatives that are highly inducible by synthetic ligands, escape inactivation and efficiently induce apoptosis. We have ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203256

    authors: Sengupta S,Ralhan R,Wasylyk B

    更新日期:2000-01-20 00:00:00

  • Novel small molecules disrupting Hec1/Nek2 interaction ablate tumor progression by triggering Nek2 degradation through a death-trap mechanism.

    abstract::Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interactio...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.67

    authors: Hu CM,Zhu J,Guo XE,Chen W,Qiu XL,Ngo B,Chien R,Wang YV,Tsai CY,Wu G,Kim Y,Lopez R,Chamberlin AR,Lee EY,Lee WH

    更新日期:2015-03-05 00:00:00

  • A SOCS-1 peptide mimetic inhibits both constitutive and IL-6 induced activation of STAT3 in prostate cancer cells.

    abstract::Prostate cancer is the second highest cause of cancer-related deaths of men in the US. Signal transducers and activators of transcription (STATs) proteins are a small family of latent cytoplasmic transcription factors that act downstream of Janus kinase (JAK) activation and mediate intracellular signaling from a wide ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208437

    authors: Flowers LO,Subramaniam PS,Johnson HM

    更新日期:2005-03-17 00:00:00

  • The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting.

    abstract::NIH sponsored a meeting of medical and veterinary pathologists with mammary gland expertise in Annapolis in March 1999. Rapid development of mouse mammary models has accentuated the need for definitions of the mammary lesions in genetically engineered mice (GEM) and to assess their usefulness as models of human breast...

    journal_title:Oncogene

    pub_type: 共识发展会议,杂志文章,评审

    doi:10.1038/sj.onc.1203277

    authors: Cardiff RD,Anver MR,Gusterson BA,Hennighausen L,Jensen RA,Merino MJ,Rehm S,Russo J,Tavassoli FA,Wakefield LM,Ward JM,Green JE

    更新日期:2000-02-21 00:00:00

  • Myc suppresses tumor invasion and cell migration by inhibiting JNK signaling.

    abstract::Tumor metastasis, but not primary overgrowth, is the leading cause of mortality for cancer patients. During the past decade, Drosophila melanogaster has been well-accepted as an excellent model to address the intrinsic mechanism of different aspects of cancer progression, ranging from tumor initiation to metastasis. I...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2016.463

    authors: Ma X,Huang J,Tian Y,Chen Y,Yang Y,Zhang X,Zhang F,Xue L

    更新日期:2017-06-01 00:00:00

  • Cdc25B activity is regulated by 14-3-3.

    abstract::In the G2 phase cell cycle checkpoint arrest, the cdc25-dependent activation of cyclin B/cdc2, a critical step in regulating entry into mitosis, is blocked. Studies in yeast have demonstrated that the inhibition of cdc25 function involves 14-3-3 binding to cdc25. In humans, two cdc25 isoforms have roles in G2/M progre...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204574

    authors: Forrest A,Gabrielli B

    更新日期:2001-07-19 00:00:00

  • The nuclear receptor TR3 regulates mTORC1 signaling in lung cancer cells expressing wild-type p53.

    abstract::The orphan nuclear receptor TR3 (NR41A and Nur77) is overexpressed in most lung cancer patients and is a negative prognostic factor for patient survival. The function of TR3 was investigated in non-small-cell lung cancer A549 and H460 cells, and knockdown of TR3 by RNA interference (siTR3) inhibited cancer cell growth...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.504

    authors: Lee SO,Andey T,Jin UH,Kim K,Singh M,Safe S

    更新日期:2012-07-05 00:00:00

  • Crosstalk between NRF2 and HIPK2 shapes cytoprotective responses.

    abstract::Homeodomain interacting protein kinase-2 (HIPK2) is a member of the HIPK family of stress-responsive kinases that modulates cell growth, apoptosis, proliferation and development. HIPK2 has several well-characterised tumour suppressor roles, but recent studies suggest it can also contribute to tumour progression, altho...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2017.221

    authors: Torrente L,Sanchez C,Moreno R,Chowdhry S,Cabello P,Isono K,Koseki H,Honda T,Hayes JD,Dinkova-Kostova AT,de la Vega L

    更新日期:2017-11-02 00:00:00

  • The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.

    abstract::Polymorphisms and somatic mutations in Flap Endonuclease 1 (FEN1), an essential enzyme involved in DNA replication and repair, can lead to functional deficiencies of the FEN1 protein and a predisposition to cancer. We identified a FEN1 germline mutation that changed residue E359 to K in a patient whose family had a hi...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.19

    authors: Chung L,Onyango D,Guo Z,Jia P,Dai H,Liu S,Zhou M,Lin W,Pang I,Li H,Yuan YC,Huang Q,Zheng L,Lopes J,Nicolas A,Chai W,Raz D,Reckamp KL,Shen B

    更新日期:2015-02-12 00:00:00

  • Phosphorylation of Helicobacter pylori CagA by c-Abl leads to cell motility.

    abstract::Helicobacter pylori induces a strong motogenic response in infected gastric epithelial host cells, which is enhanced by translocation of the pathogenic factor cytotoxin-associated gene A (CagA) into host cells via a specialized type IV secretion system. Once injected into the cytosol CagA is rapidly tyrosine phosphory...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210139

    authors: Poppe M,Feller SM,Römer G,Wessler S

    更新日期:2007-05-24 00:00:00

  • Induction of hepatocyte proliferation and liver hyperplasia by the targeted expression of cyclin E and skp2.

    abstract::Cells in culture become competent to replicate in the absence of growth factor after progressing beyond the late G1 restriction point, suggesting that a set of genes expressed during G1 phase is sufficient to trigger completion of the cell cycle. However, this has not been demonstrated in an in vivo system. In this st...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204248

    authors: Nelsen CJ,Hansen LK,Rickheim DG,Chen C,Stanley MW,Krek W,Albrecht JH

    更新日期:2001-04-05 00:00:00

  • Overexpression of miR-489 derails mammary hierarchy structure and inhibits HER2/neu-induced tumorigenesis.

    abstract::Although it has been demonstrated that transformed progenitor cell population can contribute to tumor initiation, factors contributing to this malignant transformation are poorly known. Using in vitro and xenograft-based models, previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by targeting v...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-018-0439-1

    authors: Patel Y,Soni M,Awgulewitsch A,Kern MJ,Liu S,Shah N,Singh UP,Chen H

    更新日期:2019-01-01 00:00:00

  • Adaptive upregulation of FOXD3 and resistance to PLX4032/4720-induced cell death in mutant B-RAF melanoma cells.

    abstract::Melanoma cells driven by mutant v-raf murine sarcoma viral oncogene homolog B1 (B-RAF) are highly resistant to chemotherapeutic treatments. Recent phase 1 results with PLX4032/RG7204/vemurafenib, which selectively inhibits B-RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)1...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.424

    authors: Basile KJ,Abel EV,Aplin AE

    更新日期:2012-05-10 00:00:00

  • RAN GTPase is an effector of the invasive/metastatic phenotype induced by osteopontin.

    abstract::Osteopontin (OPN) is a phosphorylated glycoprotein that binds to alpha v-containing integrins and is important in malignant transformation and cancer. Previously, we have utilized suppressive subtractive hybridization between mRNAs isolated from the Rama 37 (R37) rat mammary cell line and a subclone rendered invasive ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.325

    authors: Kurisetty VV,Johnston PG,Johnston N,Erwin P,Crowe P,Fernig DG,Campbell FC,Anderson IP,Rudland PS,El-Tanani MK

    更新日期:2008-12-04 00:00:00

  • Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation.

    abstract::Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell rec...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202411

    authors: Elly C,Witte S,Zhang Z,Rosnet O,Lipkowitz S,Altman A,Liu YC

    更新日期:1999-02-04 00:00:00

  • DNA: leukemia's secret weapon of bone mass destruction.

    abstract::Interaction of tumour cells with their microenvironment impacts on all aspects of cancer, ranging from development through to treatment response. In this issue, Dvorak and colleagues(1) reveal a novel tumour/microenvironment relationship that may drive leukemia pathogenesis. Specifically, they find that leukemic cells...

    journal_title:Oncogene

    pub_type: 评论,杂志文章

    doi:10.1038/onc.2012.639

    authors: Tait S

    更新日期:2013-10-31 00:00:00

  • Targeting AU-rich element-mediated mRNA decay with a truncated active form of the zinc-finger protein TIS11b/BRF1 impairs major hallmarks of mammary tumorigenesis.

    abstract::Altered expression of regulatory RNA-binding proteins (RBPs) in cancer leads to abnormal expression of mRNAs encoding many factors involved in cancer hallmarks. While conventional anticancer therapies usually target one pathway at a time, targeting key RBP would affect multiple genes and thus overcome drug resistance....

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-019-0784-8

    authors: Rataj F,Planel S,Denis J,Roelants C,Filhol O,Guyon L,Feige JJ,Cherradi N

    更新日期:2019-06-01 00:00:00

  • Genetic and epigenetic alterations as hallmarks of the intricate road to cancer.

    abstract::Despite the clonal origin of most tumors, their tremendous heterogeneity suggests that cancer progression springs from the combined forces of both genetic and epigenetic events, which produce variant clonal populations, together with the selective pressures of the microenvironment, which promote growth and, perhaps, d...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206955

    authors: Macaluso M,Paggi MG,Giordano A

    更新日期:2003-09-29 00:00:00

  • Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression.

    abstract::Cyclin D1, a putative G1 cyclin, has been implicated in cell cycle control. The human cyclin D1 gene is located on chromosome 11q13 where DNA rearrangement and amplification have been detected in several types of human cancer. Previous studies demonstrated that the cyclin D1 gene is not only rearranged or amplified bu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Jiang W,Kahn SM,Zhou P,Zhang YJ,Cacace AM,Infante AS,Doi S,Santella RM,Weinstein IB

    更新日期:1993-12-01 00:00:00

  • Selective loss of endogenous p21waf1/cip1 induction underlies the G1 checkpoint defect of monomeric p53 proteins.

    abstract::Wild-type p53 protein displays a spectrum of activities including the ability to suppress transformed cell growth to direct apoptotic cell death and to mediate G1 checkpoint in response to cellular DNA damage. Earlier work showed that a self-association defective p53 protein retained transformation suppressor activity...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:

    authors: Tarunina M,Grimaldi M,Ruaro E,Pavlenko M,Schneider C,Jenkins JR

    更新日期:1996-08-01 00:00:00

  • β-catenin S45F mutation results in apoptotic resistance.

    abstract::Wnt/β-catenin signaling is one of the key cascades regulating embryogenesis and tissue homeostasis; it has also been intimately associated with carcinogenesis. This pathway is deregulated in several tumors, including colorectal cancer, breast cancer, and desmoid tumors. It has been shown that CTNNB1 exon 3 mutations a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-020-1382-5

    authors: Braggio D,Zewdu A,Londhe P,Yu P,Lopez G,Batte K,Koller D,Costas Casal de Faria F,Casadei L,Strohecker AM,Lev D,Pollock RE

    更新日期:2020-08-01 00:00:00

  • Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates.

    abstract::The motility of cancer cells in 3D matrices is of two types: mesenchymal motility, in which the cells are elongated and amoeboid motility, in which the cells are round. Amoeboid motility is driven by an actomyosin-based contractile force, which is regulated by the Rho/ROCK pathway. However, the molecular mechanisms un...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.2

    authors: Yamazaki D,Kurisu S,Takenawa T

    更新日期:2009-04-02 00:00:00

  • Facilitation of adenoviral wild-type p53-induced apoptotic cell death by overexpression of p33(ING1) in T.Tn human esophageal carcinoma cells.

    abstract::To investigate the effect of p33(ING1) on wild-type p53 gene therapy, T.Tn human esophageal carcinoma cells were stably transfected with p33(ING1) cDNA. Infection with Ad-p53 (recombinant adenovirus containing wild-type p53) into p33-transfected cells reduced cell viability, while infection with empty vector had littl...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205176

    authors: Shimada H,Liu TL,Ochiai T,Shimizu T,Haupt Y,Hamada H,Abe T,Oka M,Takiguchi M,Hiwasa T

    更新日期:2002-02-14 00:00:00

  • FLI-1 inhibits differentiation and induces proliferation of primary erythroblasts.

    abstract::Friend virus-induced erythroleukemia involves two members of the ETS family of transcriptional regulators, both activated via proviral insertion in the corresponding loci. Spi-1/PU.1 is expressed in the disease induced by the original Friend virus SFFV(F-MuLV) complex in adult mice. In contrast, FLI-1 is overexpressed...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202534

    authors: Pereira R,Quang CT,Lesault I,Dolznig H,Beug H,Ghysdael J

    更新日期:1999-02-25 00:00:00

  • Inhibition of Bcl-xL expression sensitizes normal human keratinocytes and epithelial cells to apoptotic stimuli.

    abstract::The epidermis is continually exposed to harmful mutagens that have the potential to cause DNA damage. To protect the skin from accumulating mutated cells, keratinocytes have developed a highly regulated mechanism of eliminating damaged cells through apoptosis. Bcl-xL is a well-described cell survival protein that when...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202836

    authors: Taylor JK,Zhang QQ,Monia BP,Marcusson EG,Dean NM

    更新日期:1999-08-05 00:00:00

  • Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-gamma regulated gene negatively associated with prostate tumor invasion.

    abstract::The most ominous development in tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique pane...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204379

    authors: Manos EJ,Kim ML,Kassis J,Chang PY,Wells A,Jones DA

    更新日期:2001-05-17 00:00:00

  • c-Met-induced epithelial carcinogenesis is initiated by the serine protease matriptase.

    abstract::The progression and negative outcome of a variety of human carcinomas are intimately associated with aberrant activity of the c-Met oncogene. The underlying cause of this dysregulation, however, remains a subject of discussion, as the majority of cancer patients do not present with activating mutations in c-Met recept...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.586

    authors: Szabo R,Rasmussen AL,Moyer AB,Kosa P,Schafer JM,Molinolo AA,Gutkind JS,Bugge TH

    更新日期:2011-04-28 00:00:00

  • Transformation by Hras(G12V) is consistently associated with mutant allele copy gains and is reversed by farnesyl transferase inhibition.

    abstract::RAS-driven malignancies remain a major therapeutic challenge. The two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-o-tetradecanoylphorbol-13-acetate (TPA) model of mouse skin carcinogenesis has been used to study mechanisms of epithelial tumor development by oncogenic Hras. We used mice with an Hras(G12V) knock-in a...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2013.489

    authors: Chen X,Makarewicz JM,Knauf JA,Johnson LK,Fagin JA

    更新日期:2014-11-20 00:00:00