Abstract:
:Methylation-mediated silencing of G0-G1 switch gene 2 (G0S2) has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 opposes oncogene-induced transformation using G0s2-null immortalized mouse embryonic fibroblasts (MEF). G0s2-null MEFs were readily transformed with HRAS or EGFR treatment compared with wild-type MEFs. Importantly, restoration of G0S2 reversed HRAS-driven transformation. G0S2 is known to regulate fat metabolism by attenuating adipose triglyceride lipase (ATGL), but repression of oncogene-induced transformation by G0S2 was independent of ATGL inhibition. Gene expression analysis revealed an upregulation of gene signatures associated with transformation, proliferation, and MYC targets in G0s2-null MEFs. RNAi-mediated ablation and pharmacologic inhibition of MYC abrogated oncogene-induced transformation of G0s2-null MEFs. Furthermore, we found that G0S2 was highly expressed in normal breast tissues compared with malignant tissue. Intriguingly, high levels of G0S2 were also associated with a decrease in breast cancer recurrence rates, especially in estrogen receptor-positive subtypes, and overexpression of G0S2 repressed the proliferation of breast cancer cells in vitro. Taken together, these findings indicate that G0S2 functions as a tumor suppressor in part by opposing MYC activity, prompting further investigation of the mechanisms by which G0S2 silencing mediates MYC-induced oncogenesis in other malignancies.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Yim CY,Sekula DJ,Hever-Jardine MP,Liu X,Warzecha JM,Tam J,Freemantle SJ,Dmitrovsky E,Spinella MJdoi
10.1158/0008-5472.CAN-15-2265subject
Has Abstractpub_date
2016-03-01 00:00:00pages
1204-13issue
5eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-2265journal_volume
76pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Studies of V79-171 cells were undertaken to determine what extracellular or intracellular derivative of the drug WR-2721 is associated with radioprotection. The effect of preincubation at 23 +/- 1 degree C with WR-2721, and with derivatives of WR-2721 produced in medium containing alkaline phosphatase, upon survival o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::The bcl-2 family of genes code for proteins that contain anti-apoptotic or pro-apoptotic activity. The human bfl-1 gene contains an open reading frame for a 175-amino acid Bcl-2 family protein. Among the various Bcl-2 family members, the Bfl-1 protein shares the highest homology with the mouse A1 protein. These two pr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-15 00:00:00
abstract::The present study was designed to investigate the effect of selenium supplementation on dimethylbenz[a]anthracene-induced mammary tumorigenesis in female Sprague-Dawley rats fed either a 5 or 25% corn oil diet, denoted as low fat (LF) or high fat (HF), respectively. Selenium supplementation of LF and HF diets were beg...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-1617
更新日期:2016-02-15 00:00:00
abstract::Pluripotent cells within embryonal carcinoma (EC) can differentiate in vivo or in vitro on treatment with specific agents. Differentiating EC cells express lower levels of stem cell-related genes, such as Cripto-1. We show that migration of human EC cells (NTERA/2 and NCCIT) can be reduced following treatment with the...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-2985
更新日期:2009-03-01 00:00:00
abstract::Enhanced glucose and lipid metabolism is one of the most common properties of malignant cells. ATP citrate lyase (ACLY) is a key enzyme of de novo fatty acid synthesis responsible for generating cytosolic acetyl-CoA and oxaloacetate. To evaluate its role in lung cancer progression, we here analyzed ACLY expression in ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1235
更新日期:2008-10-15 00:00:00
abstract::Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacologic targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially eliminate malignant over normal cells. We previously discovered that CDK2 inhibition causes lung cancer cells with more than ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-1494
更新日期:2015-05-15 00:00:00
abstract::To identify CpG islands differentially methylated in pancreatic adenocarcinoma, we used methylated CpG island amplification (MCA) coupled with representational difference analysis. Of 42 CpG islands identified by MCA/representational difference analysis, 7 CpG islands [methylated in carcinoma of the pancreas (MICP)] w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::(+-)-2-[Hydroxy[tetrahydro-2-(octadecyloxy)methylfuran-2- yl]methoxyl]phosphinyloxy-N,N,N-trimethylethaniminium hydroxide, inner salt (SRI 62-834) is a tetrahydrofuran analogue of platelet activating factor (PAF) that is currently entering clinical trial. Like other ether lipids it is of interest as a membrane-active ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::In 10 separate experiments, mice with established chemically induced or UV light-induced skin papillomas were treated continuously with green tea in the drinking water or with i.p. injections of a green tea polyphenol fraction or (-)-epigallocatechin gallate three times a week for 4-10 weeks. Partial tumor regression ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Benzidine, a human urinary bladder carcinogen, induces hepatic tumors in mice and rats. In this study, [3H]benzidine was administered in drinking water to mice for 1 week, and the covalent binding of the carcinogen to hepatic DNA was then determined. A single carcinogen:DNA adduct was detected which decreased in conce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-07-01 00:00:00
abstract::We obtained seven monoclonal antibodies (MAb) against a gastric mucin of an ALeb patient. By immunoperoxidase on normal gastric mucosae, two MAbs (3-3A and 2-25 LE) reacted exclusively with the A and Lewis-positive individuals, respectively; the five other MAbs (1-13 M1, 2-11 M1, 2-12 M1, 9-13 M1, and 58 M1) stained t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::Imatinib currently represents the standard treatment in the early chronic phase of chronic myelogenous leukemia (CML), thanks to the high percentage of cytogenetic complete remission achieved, but it is yet unclear to what extent it can eradicate leukemia. Therefore, different vaccination strategies have been suggeste...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3737
更新日期:2007-06-01 00:00:00
abstract::Groups of 15 mice of three different laboratory strains (BALB/c, C3H/He, DBA/2) were fed on a low iron diet (5 mg iron/kg diet), and three similar groups of 15 mice were maintained on a normal iron diet (312 mg iron/kg diet). When the low iron diet group became iron deficient, tumor cells (5 x 10(5) cells/mouse) of CA...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Chinese hamster ovary cells exposed to the sulfhydryl compound cysteamine combined with heat treatment at 44 degrees C developed thermotolerance within 8 h. After initial treatment either with 15 min cysteamine (0.4 mM) at 37 degrees C immediately followed by 15 min heat at 44 degrees C or with 15 min cysteamine (0.4 ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus al...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3178
更新日期:2016-12-01 00:00:00
abstract::Hypoxia-inducible factor (HIF)-1, a heterodimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits coordinates pathophysiologic responses toward decreased oxygen availability. It is now appreciated that enhanced protein translation of HIF-1alpha under normoxia accounts for an alternative regulatory c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1437
更新日期:2004-12-15 00:00:00
abstract::DNA methylation aberrations have been implicated in acquired resistance to platinum drugs in ovarian cancer. In this study, we elucidated an epigenetic signature associated with platinum drug resensitization that may offer utility in predicting the outcomes of patients who are coadministered a DNA methyltransferase in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1492
更新日期:2018-02-01 00:00:00
abstract::In these studies, Syrian hamster embryo cells (SHE), which were isolated at different stages of neoplastic progression, were used to test the ability of the protein phosphatase inhibitors, okadaic acid and sodium orthovanadate (Na3VO4) to induce neoplastic progression. We observed that these chemicals can induce trans...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-15 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDA...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0960
更新日期:2019-11-15 00:00:00
abstract::Tumor hypoxia is associated with resistance to antiangiogenic therapy and poor prognosis. The Siah E3 ubiquitin ligases regulate the hypoxic response pathway by modulating the turnover of the master proangiogenic transcription factor hypoxia-inducible factor-1α (Hif-1α). In this study, we show that genetic deficiency ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3310
更新日期:2012-04-01 00:00:00
abstract::A physiological in vivo increase of plasma free fatty acid concentration after an overnight fast was found to be accompanied by a rise of the non-protein bound estradiol fraction. A similar increase was observed after lipase activation by the i.v. injection of 500 IU heparin in 5 healthy non-fasting subjects. In vitro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::The role of oxidative metabolism in the up-regulation/activation of stress-induciblesignaling pathways as well as induction of micronucleus formation in bystander cells was investigated. By immunoblotting and in situ immunofluorescence, active Cu-Zn superoxide dismutase (SOD) enzyme and active catalase enzyme were sho...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::The effects of in vivo administration of a pharmacologically toxic dose of the lipophilic cationic compound, MKT-077, were investigated in selected vital organs of the rat. MKT-077 (15 mg/kg body weight), administered by bolus i.v. injection every day for 5 days, did not detectably influence rat heart and kidney mitoc...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::p21(Cip1) is a cyclin-dependent kinase inhibitor whose abundance increases in cells exposed to radiation or other DNA-damaging agents. Such increases activate a G1 checkpoint, which allows time for DNA repair before S phase entry. By inhibiting cell cycle progression, p21(Cip1) potentially suppresses tumorigenesis, an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-06-15 00:00:00
abstract::The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impedes our understanding of the malignant transformation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studie...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-3880
更新日期:2005-06-01 00:00:00
abstract::The effect of rhodium(II) acetate, propionate, and methoxyacetate on the activity of 17 enzymes was evaluated. The enzymes were preincubated with the rhodium(II) complexes in order to detect irreversible inhibition. All enzymes that have essential sulfhydryl groups in or near their active site were found to be irrever...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-12-01 00:00:00
abstract::Tumor antigen-induced inhibition of leukocyte adherence was adapted and modified for use in glass test tubes for the study of cell-mediated antitumor immunity to human adenocarcinoma of the breast. Peripheral blood leukocytes from 40 to 47 patients with proven breast cancer responded to an antigenic extract of breast ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-09-01 00:00:00
abstract::The ING family of proteins is involved in the regulation of diverse processes ranging from cell cycle and cellular senescence to apoptosis. These effects are most likely through activation of acetylation-dependent pathways that ultimately alter gene expression. Despite reports linking ING to p53 activation, the molecu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-15 00:00:00