Abstract:
:Transcriptional silencing of antitumor genes via CpG island methylation could be a mechanism mediating prostate cancer (PCa) progression from an androgen-sensitive (AS) to an androgen-insensitive (AI) state. We have used the methylation-sensitive restriction fingerprinting (MSRF) technique to identify novel CpG-rich sequences that are differentially methylated between the genome of the AS PCa cell line LNCaP and that of an AI subline LNCaP(CS) generated by maintaining LNCaP in medium with charcoal-stripped (CS) serum for over 30 passages. One such sequence identified was located on a 5' CpG island that was found to span part of the promoter, exon 1, and part of intron 1 of the peroxisomal membrane protein 24 kDa (PMP24) gene. Using semiquantitative RT-PCR and bisulfite genomic sequencing, we established an inverse relationship between mRNA expression and methylation of the 5' CpG island of PMP24. PMP24 mRNA was absent in LNCaP(CS) and the androgen receptor-negative PC-3 cell line; both exhibited dense methylation in the said CpG island. In contrast, PMP24 mRNA was expressed in LNCaP and normal prostatic epithelial cells (NPrECs) whose PMP24 5' CpG island remained unmethylated. Treatment of LNCaP(CS) and PC-3 with the demethylating agent 5-aza-2'-deoxycytidine (5-AZAdC) reactivated PMP24 mRNA expression. Transient transfection of PMP24 into LNCaP(CS) and PC-3 cells induced a significant reduction in cell growth and soft-agar colony formation potential, suggesting that PMP24 gene product has antitumor properties. These results demonstrate the utility of MSRF in the identification of novel, differentially methylated DNA sequences in the genome and suggest that hypermethylation-mediated silencing of PMP24 is an epigenetic event involved in PCa progression to androgen independence.
journal_name
Oncogenejournal_title
Oncogeneauthors
Wu M,Ho SMdoi
10.1038/sj.onc.1207076subject
Has Abstractpub_date
2004-01-08 00:00:00pages
250-9issue
1eissn
0950-9232issn
1476-5594pii
1207076journal_volume
23pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The p53 family of proteins play instrumental roles in mediating the cellular response to stress. The p53-related gene product, p73, occurs as two distinct protein isoforms, referred to as alpha and beta, which differ in the length of the C-terminal region and arise through alternative splicing of the p73 RNA. Here, we...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202793
更新日期:1999-07-22 00:00:00
abstract::Ferritin is the major intracellular iron storage protein that sequesters excess free iron to minimize generation of iron-catalysed reactive oxygen species. We previously demonstrated that expression of ferritin heavy chain (ferritin H) was induced by pro-oxidants, which is a part of cellular antioxidant response to pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208901
更新日期:2005-11-17 00:00:00
abstract::We determined whether proteins encoded by the nm23/nucleoside diphosphate (NDP) kinase gene, a potential metastasis-suppressor gene, are expressed on the cell surface. Monoclonal antibodies (mAb) specific for nm23-H1 or H2 proteins were prepared using the corresponding fusion proteins with glutathione S-transferase (G...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::FUS (also called TLS), EWSR1 and TAF15 (also called TAF2N) are related genes involved in tumor type-specific fusion oncogenes in human malignancies. The FUS-DDIT3 fusion oncogene results from a t(12;16)(q13;p11) chromosome translocation and has a causative role in the initiation of myxoid/round cell liposarcomas (MLS/...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.378
更新日期:2009-01-15 00:00:00
abstract::The E2F1 transcription factor, which is deregulated in most human cancers by mutations in the p16-cyclin D-Rb pathway, has both oncogenic and tumor-suppressive properties. This is dramatically illustrated by the phenotype of an E2F1 transgenic mouse model that spontaneously develops tumors in the skin and other epithe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209120
更新日期:2006-02-09 00:00:00
abstract::An early event of cell migration is characterized as the rapid reorganization of the actin cytoskeleton. Recently, we have demonstrated that rapamycin inhibits tumor cell motility. To understand the underlying mechanism, this study was set to determine whether rapamycin inhibition of cell motility is related to its pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.137
更新日期:2008-08-28 00:00:00
abstract::In the search for retinoids active against Burkitt's lymphoma (BL), we found that the arotinoid mofarotene (Ro 40-8757) induced strong antiproliferative and apoptotic responses in most established BL cell lines as well as in primary BL cells. Ro 40-8757-induced apoptosis is associated with mitochondrial membrane depol...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206060
更新日期:2003-02-13 00:00:00
abstract::Accumulating evidences have shown the association between aberrantly expressed microRNAs (miRs) and cancer, where these small regulatory RNAs appear to dictate the cell fate by regulating all the main biological processes. We demonstrated the responsibility of the circuitry connecting the oncomiR-221&222 with the tumo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.357
更新日期:2016-06-09 00:00:00
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
更新日期:1999-08-05 00:00:00
abstract::Whole chromosome instability (W-CIN) is a hallmark of human cancer and contributes to the evolvement of aneuploidy. W-CIN can be induced by abnormally increased microtubule plus end assembly rates during mitosis leading to the generation of lagging chromosomes during anaphase as a major form of mitotic errors in human...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-01524-4
更新日期:2021-01-01 00:00:00
abstract::Arsenite trioxide (As2O3) induces apoptosis in several cell lines by disturbing key signal transduction pathways through its oxidative properties. Here, we report that As2O3 also induces the phosphorylation of the retinoid receptor RXRalpha, subsequent to oxidative damages and the activation of the stress-activated pr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208402
更新日期:2005-03-31 00:00:00
abstract::Low dose treatment with the DNA methylation inhibitor decitabine has been shown to be applicable for the management of certain types of cancer. However, its antitumor effect and mechanisms are context dependent and its activity has never been systematically studied in bladder cancer treatment. We used mouse models, cu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-0799-1
更新日期:2019-07-01 00:00:00
abstract::Emerging evidence has shown that cancer stem cells (CSCs) are the cellular determinants to promote cancer invasion and metastasis. However, the mechanism underlying CSC invasion remains unknown. MicroRNAs are evolutionally conserved small noncoding RNAs that are critical for the regulation of gene expression, and thei...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.75
更新日期:2015-03-12 00:00:00
abstract::Ovarian endometrioid adenocarcinomas (OEAs) frequently exhibit constitutive activation of canonical WNT signaling, usually as a result of oncogenic mutations that stabilize and dysregulate the β-catenin protein. In previous work, we used microarray-based methods to compare gene expression in OEAs with and without dysr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.123
更新日期:2011-10-06 00:00:00
abstract::Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207063
更新日期:2003-11-20 00:00:00
abstract::Here we show that pemetrexed-treated mesothelioma cells undergo accelerated senescence. This is characterized by the secretion of proinflammatory and mitogenic cytokines, reminiscent of an SASP (senescence-associated secretory phenotype). Conditioned media from senescent MPM (malignant pleural mesothelioma) cells trig...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.485
更新日期:2012-06-28 00:00:00
abstract::Integrins are adhesion receptors that mediate both cell-extracellular matrix and cell-cell interactions. It has also been reported that the loss of integrin alpha4 expression might be associated with metastasis in several cancers. However, the molecular mechanism for loss of their expression in cancers has not been ex...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207470
更新日期:2004-04-22 00:00:00
abstract::DNA double-strand breaks (DSBs), the most hazardous DNA lesions, may result in genomic instability, a hallmark of cancer cells. The main DSB repair pathways are non-homologous end joining (NHEJ) and homologous recombination (HR). In mammalian cells, NHEJ, which can lead to inaccurate repair, predominates. HR repair (H...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.516
更新日期:2012-07-26 00:00:00
abstract::The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) is an important component of the cell cycle and inactivation of the gene has been found in a variety of human cancers. In order to investigate the role of p16 gene in the tumorigenesis of hepatocellular carcinoma (HCC), 48 cases of HCC were analysed for p16 alterations...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202359
更新日期:1999-01-21 00:00:00
abstract::Cells are under constant attack from genotoxins and rely on a multifaceted DNA damage response (DDR) network to maintain genomic integrity. Central to the DDR are the ATM and ATR kinases, which respond primarily to double-strand DNA breaks (DSBs) and replication stress, respectively. Optimal ATR signaling requires the...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.118
更新日期:2016-02-04 00:00:00
abstract::To explore the molecular mechanisms by which retinoic acid inhibits oncogenic transformation, we have examined the effects of retinoic acid on the polyomavirus-induced transformation of rat fibroblasts. Treatment of rat F111 fibroblasts with high concentrations of retinoic acid (10(-6) M) partially inhibited the abili...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modifications that contribute to malignant progression in the GC remain poorly defined. Recently, a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210211
更新日期:2007-06-21 00:00:00
abstract::The C-terminal src kinase (Csk) is responsible for the phosphorylation of the carboxy-terminal tyrosine of several tyrosine kinases of the Src family. This phosphorylation site has a negative regulatory function. Csk is unique among the members of the protein tyrosine kinase family because it lacks the conserved tyros...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-05-01 00:00:00
abstract::Tamoxifen (Tam), besides its action as an anti-estrogen, also inhibits cell proliferation of estrogen receptor (ER)-negative cancer cells by an unknown mechanism. In this study, we used ER-negative lung cancer cells to clarify such ER-independent inhibitory effect of Tam. We found that Tam induced G1 growth arrest in ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202755
更新日期:1999-07-22 00:00:00
abstract::Tumor suppressor genes and the immune system are critical players in inhibiting cancer initiation and/or progression. However, little is known about whether a tumor suppressor gene can function through both immune-dependent and -independent mechanisms. Retinoic acid receptor responder 2 (RARRES2) is transcriptionally ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.497
更新日期:2017-06-22 00:00:00
abstract::cDNA clones of the ski-related gene, sno, were isolated from a chicken cDNA library and sequenced. In contrast to the human system, from which two forms of sno cDNAs have been isolated, we obtained only one type of chicken sno cDNA, that encoding snoN. The coding region for chicken snoN was inserted into the retrovira...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Resistance to detachment-induced apoptosis, a process commonly referred as anoikis, is emerging as a hallmark of metastatic malignancies, mainly because it can ensure anchorage-independent growth and survival during organ colonization. Besides, a sustained oxidative stress has been associated with several steps of car...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.77
更新日期:2009-05-21 00:00:00
abstract::Several lines of evidence suggest that gastrin and the CCK-2 receptor (CCK2R) could contribute to pancreatic carcinogenesis by modulating processes such as proliferation, cell adhesion or migration. In the current study, we used a 'cancer gene array' and identified beta1-integrin subunit as a new gastrin-regulated gen...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209484
更新日期:2006-07-27 00:00:00
abstract::Leukemogenesis requires two classes of mutations, one that promotes proliferation and one that blocks differentiation. The erythroleukemia induced by Friend virus is a multistage disease characterized by an early proliferative stage driven by the interaction of the viral glycoprotein, gp55, with Sf-Stk and the EpoR, a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.202
更新日期:2009-09-24 00:00:00
abstract::Growth factor receptor-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. In this study, we delineated a pathway that involves HER2/PI-3K/Akt in mediating multidrug resistance in human breast cancer cells. We found that the cell lines that express bo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206394
更新日期:2003-05-22 00:00:00