Abstract:
:14-3-3sigma proteins regulate numerous cellular processes that are important to cancer development. One of its biological roles involves G2 cell-cycle arrest following DNA damage. It has also been reported that the loss of 14-3-3sigma expression via CpG methylation may contribute to malignant transformation by impairing the G2 cell-cycle checkpoint function, thereby allowing an accumulation of genetic defects. However, how the CpG methylation-dependent silencing mechanism works in relation to promoter methylation associated with methyl-CpG-binding proteins (MeCPs) is still unclear. To better understand the mechanism, we first examined the methylation status of the 14-3-3sigma promoter-associated CpG islands and 14-3-3sigma gene expression in a subset of prostate cancer cell lines using methylation-specific PCR (MSP), an HhaI-based DNA methylation assay, and reverse transcription-PCR (RT-PCR). We found that the 14-3-3sigma expression is lost in LNCaP and Tramp-C1 prostate cancer cell lines and that this expression is restored after treatment with epigenetic silencing modifiers 5-aza-2'-deoxycytidine (5-aza) and trichostatin A (TSA). These results imply transcriptional silencing via promoter-associated CpG methylation. Chromatin immunoprecipitation analysis revealed that methyl-CpG-binding protein 2 (MBD2) is associated preferentially to the methylated CpG island in the 14-3-3sigma promoter in LNCaP and Tramp-C1 cells but not in 14-3-3sigma-expressing PC3 and DU145 cells, which contain an unmethylated CpG island in the 14-3-3sigma promoter region. The 14-3-3sigma gene silencing because of CpG methylation correlates with binding of MBD2. In addition, the activation of 14-3-3sigma gene expression by a combination of 5-aza and TSA also involves the release of the MBD2 from the 14-3-3sigma promoter-methylated CpG island in LNCaP and Tramp-C1 cells. Furthermore, MBD2 knockdown by siRNA stimulated 14-3-3sigma expression in LNCaP cells. We also investigated whether the loss of 14-3-3sigma expression in LNCaP and Tramp-C1 cells affects cell proliferation by MTT assays. Interestingly, we observed that 14-3-3sigma-inactivated LNCaP and Tramp-C1 cells had markedly decreased cell proliferation and protein expression of proliferation cell nuclear antigen (PCNA) after restoration of 14-3-3sigma expression with 5-aza and TSA treatment. On the other hand, the same treatment did not significantly affect 14-3-3sigma-active PC3 and DU145 cells, which normally express 14-3-3sigma. Finally, 14-3-3sigma knockdown by siRNA resulted in increased proliferation in PC3 and DU145 cells. These findings suggest that the transcriptional silencing of the 14-3-3sigma gene is caused by promoter CpG island methylation associated with MBD2, and that this may play an important role in prostate cancer progression during the invasive and metastatic stages of the disease.
journal_name
Oncogenejournal_title
Oncogeneauthors
Pulukuri SM,Rao JSdoi
10.1038/sj.onc.1209462subject
Has Abstractpub_date
2006-08-03 00:00:00pages
4559-72issue
33eissn
0950-9232issn
1476-5594pii
1209462journal_volume
25pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::A protein of 300 kDa (p300) associates with the adenovirus E1A proteins and has been implicated in the control of cell cycle progression. In mammalian cells, p300 is actively phosphorylated in both quiescent and proliferating cells and its level of phosphorylation increases as it travels from late G1 into M phase. E1A...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Snail1 is a master regulator of the epithelial-mesenchymal transition (EMT) and has been implicated in key tumor biological processes such as invasion and metastasis. It has been previously shown that poly(ADP-ribose) polymerase-1 (PARP-1) knockdown, but not PARP inhibition, downregulates the expression of Snail1. In ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.153
更新日期:2011-10-20 00:00:00
abstract::The viability of rat embryo cells immortalized by thermosensitive mutants of SV40 or polyoma Large T antigen is impaired at the non-permissive temperature thus demonstrating that the immortal phenotype is dominantly maintained by Large T antigens. We have observed that exposing these cells to the restrictive temperatu...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Our previous studies suggested that chromosome 8p deletion is associated with metastasis of hepatocellular carcinoma (HCC), in which some novel metastasis suppressor genes might be harbored. The present study aimed to identify the metastatic suppressor gene(s). A cDNA chip was constructed with the expressed sequence t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209191
更新日期:2006-03-16 00:00:00
abstract::Although established cell lines can be transformed with oncogenic ras, primary epithelial cells cannot, but require the coexpression of an immortalizing oncogene, such as the E1A region of adenovirus. We have previously shown that immortalization of primary epithelial cells by E1A 12S requires the expression of five r...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-12-19 00:00:00
abstract::Prevention and treatment options for hepatocellular carcinoma (HCC) are presently limited, underscoring the necessity for further elucidating molecular mechanisms underlying HCC development and identifying new prevention and therapeutic targets. Here, we demonstrate a unique protumorigenic niche in the livers of Ncoa5...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-020-1256-x
更新日期:2020-05-01 00:00:00
abstract::Heregulins are a group of growth factors that play diverse and critical roles in the signaling network of the human epidermal growth factor receptor (HER or EGFR) superfamily. Our earlier studies have shown that recombinant heregulinbeta1 (HRG) induces apoptosis in SKBr3 breast cancer cells that overexpress HER2. Here...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205039
更新日期:2001-12-13 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::The epithelium-specific transcription factor, ERT/ESX/ESE-1/ELF3, binds to the TGF-beta RII promoter in a sequence specific manner and regulates its expression. In this study, we investigated whether ERT could regulate endogenous TGF-beta RII expression in Hs578t breast cancer cells. Analyses of the Hs578t parental ce...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203252
更新日期:2000-01-06 00:00:00
abstract::Wild-type human p53 protein is able to self-associate and consists predominantly of homotetramers in solution. In earlier work we identified the protein sequence motifs involved in p53 quaternary structure and showed that while monomeric p53 protein retains tumour suppressor function, monomeric tumour mutant p53 lacks...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::The Epstein-Barr virus (EBV) encoded latent membrane protein, LMP1, is oncogenic in rodent fibroblasts and is an essential effector protein in EBV-induced growth-transformation of human B lymphocytes. Previous structure-function studies with LMP1 have relied largely on rodent fibroblast transformation as a functional ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-02-02 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::SCL, GATA-1, GATA-2 and GATA-3 encode lineage restricted haemopoietic transcription factors. We have previously shown that SCL, GATA-1 and GATA-2 are expressed in multipotent progenitors prior to lineage commitment, but are down-regulated during granulocyte/monocyte differentiation. The phenomenon of gene extinction i...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-02-16 00:00:00
abstract::The molecular interactions implicated in the mammalian G1/S cell cycle phase transition comprise a highly nonlinear network which can produce seemingly paradoxical results and make intuitive interpretations unreliable. A new approach to this problem is presented, consisting of (1) a convention of unambiguous reaction ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201608
更新日期:1998-02-26 00:00:00
abstract::Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a pla...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202341
更新日期:1999-01-21 00:00:00
abstract::Members of the Wnt family induce mouse mammary tumors and partially transform mammary epithelial cells in culture. However, their mechanism of transformation remains to be elucidated. In NIH3T3 mouse embryo fibroblasts, a standard transformation model, Wnt-1 and Wnt-2 were shown to induce altered properties including ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201797
更新日期:1998-05-28 00:00:00
abstract::The rodent S100-related calcium-binding protein, S100A4 induces metastasis in non-metastatic rat and mouse benign mammary cells and co-operates with benign-tumour-inducing changes in two transgenic mouse models, to yield metastatic mammary tumours. Co-transfection of the human gene for S100A4 with pSV2neo into the ben...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201948
更新日期:1998-07-30 00:00:00
abstract::Signal transduction and activator of transcription 3(STAT3) signaling is constitutively activated in various tumors, and is involved in cell survival and proliferation during oncogenesis. There are few reports, however, on the role of STAT3 signaling in gastric cancer. The aim of the present study was to clarify the r...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207606
更新日期:2004-06-17 00:00:00
abstract::Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206106
更新日期:2003-02-06 00:00:00
abstract::To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppres...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-12-21 00:00:00
abstract::Wild-type (wt) p53 acts as a tumor suppressor, while certain mutant type (mt) p53 may exhibit 'oncogenic' function. We have recently demonstrated that human papillomavirus type 18 (HPV-18) E6 can partially overcome the growth-suppressive effects of wt p53, but it remains unclear what role p53 plays in cervical carcino...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that β1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph n...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.116
更新日期:2015-04-02 00:00:00
abstract::Myxoid and round-cell liposarcomas share the translocation t(12;16)(q13;p11) creating the TLS-CHOP fusion gene as a common genetic alteration. We previously reported several unique characteristics of genomic sequences around the breakpoints in the TLS and CHOP loci, and among them was the presence of consensus recogni...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203943
更新日期:2000-11-23 00:00:00
abstract::Treatment of many cancers relies on the combined action of several genotoxins, but the detrimental effect of these drugs on normal cells can cause severe side effects. One major challenge in anticancer therapy is therefore to increase the selectivity of current treatments toward cancer cells in order to spare normal c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207999
更新日期:2004-11-25 00:00:00
abstract::Fatty acid binding protein 4 (FABP4) is a fatty acid chaperone, which is induced during adipocyte differentiation. Previously we have shown that FABP4 in endothelial cells is induced by the NOTCH1 signalling pathway, the latter of which is involved in mechanisms of resistance to antiangiogenic tumour therapy. Here, we...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.256
更新日期:2017-02-16 00:00:00
abstract::Tumor cells, stromal cell compartment and the extracellular matrix (ECM) together generate a multifaceted tumor microenvironment. Matrix metalloproteinases and their tissue inhibitors (TIMPs) provide a means for tumor-stromal interaction during tumorigenesis. Among TIMPs, TIMP-3 is uniquely localized to the ECM and is...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209104
更新日期:2006-01-26 00:00:00
abstract::The family of tripartite-motif (TRIM) proteins are involved in diverse cellular processes, but are often characterized by critical protein-protein interactions necessary for their function. TRIM16 is induced in different cancer types, when the cancer cell is forced to proceed down a differentiation pathway. We have id...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.340
更新日期:2010-11-18 00:00:00
abstract::Bcl-2 is a key inhibitor of a broad range of apoptotic pathways, yet neither the mechanism of action nor the role of Bcl-2 subcellular localization are well understood. The subcellular localization of Bcl-2 includes the mitochondrial membrane as well as the contiguous membrane of the endoplasmic reticulum and nuclear ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202716
更新日期:1999-06-10 00:00:00
abstract::A33 antigen is a membrane-bound protein that is expressed only in intestinal epithelium and in most human colon cancers. Thus, A33 antigen has been explored as a potential therapeutic target for the treatment of colon cancers. However, little is known about the mechanism responsible for the tissue-specific pattern of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206508
更新日期:2003-07-10 00:00:00
abstract::Previous studies have documented that Tumor necrosis factor alpha (TNFalpha) is a potent negative regulator of normal hematopoiesis. However, the mechanism by which TNFalpha acts at the cellular level is not totally understood. Although apoptotic cell killing appears to be the most common cellular effect of TNFalpha, ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208024
更新日期:2004-09-30 00:00:00