Abstract:
:Mdm2 (murine double minute 2) is an oncogene, first identified in BALB/c 3T3 cells. Over-expression and gene amplification of Mdm2 were found in a variety of human cancers. Recently, Mdm2 was found to be an E3 ubiquitin ligase that promotes degradation of p53, which contributes significantly to its oncogenic activity. In this study, we test a hypothesis that Mdm2 ligase dead mutants, which retained p53 binding activity but lost degradation activity, would act in a dominant negative manner to re-activate p53, especially upon stressed conditions. Five Mdm2 constructs expressing wild-type and E3 ligase-dead Mdm2 proteins were generated in a Tet-Off system and transfected into MCF-7 breast cancer cells (p53+/+ with Mdm2 overexpression) as well as MCF10A immortalized breast cells (p53+/+ without Mdm2 overexpression) as a normal control. We found that expression of Mdm2 mutants were tightly regulated by doxycycline. Withdrawal of doxycycline in culture medium triggered overexpression of Mdm2 mutants. However, expression of ligase dead mutants in MCF7 and MCF10A cells did not reactivate p53 as shown by a luciferase-reporter transcription assay and Western blot of p53 and its downstream target p21 under either unstressed condition or after exposure to DNA damaging agents. Biologically, over-expression of Mdm2 mutants had no effect on p53-induced apoptosis following DNA damage. Interestingly, over-expression of Mdm2 mutants promoted growth of MCF7 tumor cells probably via a p53-independent mechanism. Over-expression of Mdm2 mutants, however, had no effect on the growth of normal MCF10A cells and did not cause their transformation. Thus, ligase dead mutants of Mdm2 did not act in a dominant negative manner to reactivate p53 and they are not oncogenes in MCF10A cells.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Swaroop M,Sun Ysubject
Has Abstractpub_date
2003-07-01 00:00:00pages
3167-74issue
4eissn
0250-7005issn
1791-7530journal_volume
23pub_type
杂志文章abstract::The effects induced by a low dose cyclophosphamide treatment (CPA) along with an attempt of estradiol-17-beta (E2) cell recruitment, on the bioenergetics and the phosphomonoesters/phosphodiesters (PME/PDE) ratio in the transplantable MXT mouse mammary tumor have been studied by 31P-NMR spectroscopy in vivo. Our result...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::In human colorectal tissue samples, the gene expressions of 4 coactivators, p300, pCAF, TIF-2 and TRAP 220, and 7 corepressors, N-CoR, REA, MTA1, MTA1L1, HDAC1, HDAC2 and HDAC3, linked to estrogen receptors (ER), were revealed by traditional RT-PCR. Cofactors ERalpha, ERbeta and ERRalpha mRNA levels were then measured...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2005-11-01 00:00:00
abstract:BACKGROUND/AIM:3,4',7-O-trimethylquercetin (34'7TMQ), a derivative of quercetin, inhibited ovarian cancer cell migration and invasion without affecting proliferation. In this study, the apoptotic effect of 34'7TMQ on three cancer cell lines (CRL-1978, CRL-11731, SK-OV-3) was evaluated. MATERIALS AND METHODS:Expression...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12835
更新日期:2018-09-01 00:00:00
abstract::We have studied the effects of PAI-1 on the formation of metastasis using human fibrosarcoma cells and DNA transfection. A clone (1-3C), which shows low constitutive expression of PAI-1 and low metastatic potential to the lung, was selected from human fibrosarcoma cell line HT-1080. Newly-derived clones transfected wi...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::Phorbol ester, 12-0-Tetradecanoyl-13-Phorbol-Acetate (TPA), induces a terminal macrophage-like differentiation of cells from human acute myelogenous leukemia cell lines. We report here that blastoid cells obtained from acute nonlymphocytic leukemia (M1-M2) undergo differentiation-related changes characteristic of macr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-01 00:00:00
abstract:UNLABELLED:The pharmacology of progestins includes actions initiated by various cellular targets, including classic receptors characterized as nuclear transcription factors (nPR), G-protein-coupled membrane receptors (mPR), enzymes, membrane channels and transporters. The effects initiated by targets other than nPR are...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND/AIM:Novel treatment strategies aiming to eliminate or attenuate the invasive phenotype of glioblastoma multiforme (GBM), the most common and aggressive primary brain tumor, could offer a profound therapeutic benefit to patients. We previously demonstrated one method to create invasive sub-populations of GBM ...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2015-06-01 00:00:00
abstract:BACKGROUND/AIM:SLC9A9 plays an oncogenic role in esophageal squamous carcinoma and glioblastoma. Herein, we showed an oncogenic function of SLC9A9 in colorectal cancer (CRC). MATERIALS AND METHODS:We examined SLC9A9 expression in CRC specimens by immunohistochemistry. In CRC tissues, the relationship between SLC9A9 ex...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.11562
更新日期:2017-05-01 00:00:00
abstract::Methyl-tertiary-butyl ether (MTBE) is a ubiquitous oxygen-bearing additive used to reduce engine knocking and obtain cleaner gasoline combustion. Conflicting data have been reported about a possible carcinogenic role of MTBE in humans. In this study we evaluated the effects of MTBE on cell growth and transformation in...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract::We examined the expression of survivin using immunohistochemistry in 102 cases of laryngeal squamous cell carcinoma (LSCC). Overall, 65.7% (67 out of 102) of tumors were positive for survivin expression and significantly associated with tumor site, poor differentiation, tumor size, lymph node metastasis and advanced s...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:Despite a substantial body of epidemiological evidence, there is only a limited indication that gonadotropins and steroids have growth regulating functions in ovarian cancer. To elucidate the role of gonadotropins in regulating steroid metabolism in human ovarian cancer, we analyzed the modulation of estradi...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-01 00:00:00
abstract::D-penicillamine (PSH) is a copper chelator that generates hydrogen peroxide and inhibits neovascularization. As hydrogen peroxide is toxic to some tumor cells and to blood vessels, we reasoned that PSH plus copper would inhibit tumors in vivo and in vitro. To test this hypothesis, we first incubated murine J558L plasm...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract:BACKGROUND:Studies have recommended a 21-gene recurrence score (RS) to optimize adjuvant treatment for patients with early-stage breast cancer (EBC) with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) tumors. This study aimed to prospectively evaluate the impact of this RS...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.11851
更新日期:2017-08-01 00:00:00
abstract::To activate the cancerous genetic information in the cell one has either to activate oncogenes or to inactivate antioncogenes (cancerous growth suppressing genes). These processes usually happen in the cell with the aid of external factors, especially chemical carcinogens' and radiations. It was shown with the aid of ...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:1994-01-01 00:00:00
abstract::Intravenous administration of sodium benzylideneascorbate (SBA) rapidly necrotized inoperable human lung cancer, and induced degeneration of 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatocellular carcinoma (vacuolar, eosinophilic degeneration, nuclear debris) without affecting the serum glutamic oxaloacetic tr...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
abstract:PURPOSE:Effectiveness of a new device inserted within the common cellulose acetate cigarette filter (named hypobaric chamber tar-removing system, HCTRS) to remove tar and its carcinogenic compounds from mainstream cigarette smoke (MCS). METHODS:Eighty HCTRS prototypes were mounted inside the cellulose acetate filter o...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract:AIM:To evaluate the efficacy and toxicities of cisplatin and daily oral etoposide in patients with recurrent cervical cancer. PATIENTS AND METHODS:Treatment was initiated with oral etoposide 25 mg/day for 21 consecutive days, with intravenous cisplatin at 50 mg/m², on day 1, every 4 weeks, then the etoposide dose was ...
journal_title:Anticancer research
pub_type: 杂志文章,多中心研究
doi:
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:Natural killer (NK) cells are a third population of lymphocytes that can kill certain tumor cells. This killing is regulated by signals received through activating and inhibitory receptors. 2B4 (CD244), a member of the CD2 subset of Immunoglobulin superfamily, was identified as an activating receptor on NK c...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-01 00:00:00
abstract::This review focuses on the relationship between pre-treatment immune parameter values and outcome of immunotherapy of cancer patients. The evidence presented in this review suggests that there is a relationship between pre-treatment immune parameter values and survival of cancer patients treated with immunotherapy. Tu...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2011-02-01 00:00:00
abstract:BACKGROUND/AIM:Surgical resection for esophageal cancer has remained the gold-standard therapy provided worldwide. Subcarinal lymph-nodes are classified as peri-esophageal nodes and their dissection may be performed during a 2- or 3-stage esophagectomy. The necessity and prognostic value of subcarinal lymphadenectomy i...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.13594
更新日期:2019-08-01 00:00:00
abstract:AIM:To investigate whether the negative quality of life result of a large randomized exercise intervention study (BREX) was due to considerable spontaneous recovery after adjuvant treatments. PATIENTS AND METHODS:The change in QoL was studied in the control patients of the BREX study (Group 1) and a group of similar f...
journal_title:Anticancer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:
更新日期:2014-03-01 00:00:00
abstract:BACKGROUND:Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors. Recently, evidence for a viral cause has been postulated, possibly SV40 or more likely cytomegalovirus (CMV). One report indicate...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2011-03-01 00:00:00
abstract::The present study was performed to investigate the prognostic impact of tumor resection on survival in children and adolescents with malignant gliomas. From the HIT-GBM data base of the Gesellschaft für Paediatrische Onkologie und Haematologie (GPOH), 85 pediatric patients with malignant non-pontine gliomas were analy...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Tyrosine kinase inhibitors (TKIs) directed against epidermal growth factor receptor (EGFR) are important in the treatment of non-small cell lung cancer (NSCLC), especially those harboring EGFR mutations. But little is known regarding the clinical value of serum tumor marker levels measured prior to treatment...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.12018
更新日期:2017-10-01 00:00:00
abstract::Novel treatment strategies for cancer that are based on a more detailed understanding over the tumor biology are based on the latest new technology and are expected to improve the current treatment outcome for patients with cancer. However, many of these strategies still have one common and critical problem, being the...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:
更新日期:2014-08-01 00:00:00
abstract::Chronic treatment with Sasa Health, extract of bamboo grass leaves obtained by alkaline hydrolysis, in drinking water at the concentration of 0.044%-0.088% Fe-Chlorophyllin Na resulted in the significant inhibition of both development and growth of spontaneous mammary tumours in a high mammary tumour strain of SHN vir...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND/AIM:Leiomyosarcoma is an extremely rare, small bowel neoplasm (2% of all gastrointestinal tumours). Early diagnosis is challenging due to the slow growth of the cancer. The biological behaviour of this group of tumours is aggressive, and the first-line treatment is surgical resection. PATIENTS AND METHODS:T...
journal_title:Anticancer research
pub_type: 杂志文章
doi:10.21873/anticanres.14420
更新日期:2020-07-01 00:00:00
abstract::The continuity of the subepithelial band of lamina propria-indigenous macrophages (SBLP-M) discourages commensal gut bacteria from invading the host. In this Review we analyzed the impact of a disintegrating SBLP-M in inflammatory bowel disease (IBD), which results in microbiota inflow, inadequate immune responses and...
journal_title:Anticancer research
pub_type: 杂志文章,评审
doi:10.21873/anticanres.12664
更新日期:2018-07-01 00:00:00
abstract:BACKGROUND:Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast tumors and these breast tumors are usually aggressive and highly metastatic. Unfortunately, treatment options for TNBCs are limited; we have identified a novel molecule, 2'-3'-dehydrosalannol (DHS) and in this study we investigated the an...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2012-07-01 00:00:00
abstract::Several signaling pathways have been recognized in normal c-kit-mediated signal transduction following stem cell factor (SCF) stimulation including Janus kinase (JAK)/signal transducer and activator of transcription (STAT), mitogen-activated protein kinase (MAPK) and phosphoinositol 3-kinase (PI-3 K) pathways. In gast...
journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00