Abstract：
:Activation of apoptosis is believed to be critical for the role of p53 as a tumor suppressor. Here, we report a new mouse strain carrying a human p53 transgene in the mouse p53-null background. Expression of human p53 in these mice was comparable with wild-type murine p53; however, transactivation, induction of apoptosis, and G(1)-S checkpoint, but not transrepression or regulation of a centrosomal checkpoint, were deregulated. Although multiple functions of p53 were abrogated, mice carrying the human p53 transgene did not show early onset of tumors as typically seen for p53-null mice. In contrast, human p53 in the p53-null background did not prevent accelerated tumor development after genotoxic or oncogenic stress. Such behavior of human p53 expressed at physiologic levels in transgenic cells could be explained by unexpectedly high binding with Mdm2. By using Nutlin-3a, an inhibitor of the interaction between Mdm2 and p53, we were able to partially reconstitute p53 transactivation and apoptosis in transgenic cells. Our findings indicate that the interaction between p53 and Mdm2 controls p53 transcriptional activity in homeostatic tissues and regulates DNA damage- and oncogene-induced, but not spontaneous, tumorigenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Dudgeon C,Kek C,Demidov ON,Saito S,Fernandes K,Diot A,Bourdon JC,Lane DP,Appella E,Fornace AJ Jr,Bulavin DVdoi
10.1158/0008-5472.CAN-05-2063subject
Has Abstractpub_date
2006-03-15 00:00:00pages
2928-36issue
6eissn
0008-5472issn
1538-7445pii
66/6/2928journal_volume
66pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Acquired resistance to cisplatin has been generated in vitro in two human ovarian carcinoma cell lines: 41M, established from a previously untreated patient; and CH1, from a patient previously treated with cisplatin and cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin). In neither cell line with acq...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-07-15 00:00:00
abstract：:We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythro...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:Aniline of unknown purity has been reported to induce spleen hemangiosarcoma in rats. Aniline has been found to be negative in terms of mutagenicity in both bacteria and yeasts. We have found that both commercial (already rather pure) and repurified aniline are clearly positive to a similar extent in inducing DNA dama...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
abstract：:The mutational spectrum of the p53 gene was analyzed in 53 hepatocellular carcinomas. Somatic mutations of the p53 gene were detected in 17 cases (32%). Among these 17 mutations, 9 were missense mutations; the mutations in the other 8 cases were nonsense mutations, deletions, or mutations at the intron-exon junctions....
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-01-15 00:00:00
abstract：:Vinblastine was incubated in 0.2 M glycine buffer (pH 7.4 or 8.8) containing bovine serum albumin (1%) at 37 degrees C for 72 h. The reaction mixture was extracted with CH2Cl2, and the extract gave 6 major peaks (A, B, C, D, E, and F) with retention times of 5.0, 7.5, 11.0, 13.0, 23.0, and 30.0 min, respectively, in a...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:Chemoprevention, especially through the use of naturally occurring phytochemicals capable of impeding the process of one or more steps of carcinogenesis process, is a promising approach for cancer management. Despite promising results in preclinical settings, its applicability to humans has met with limited success la...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-3978
更新日期：2009-03-01 00:00:00
abstract：:In an attempt to approach the mechanism by which estrogen and antiestrogen regulate the growth of estrogen receptor-positive breast cancer, we have studied the effects of the antiestrogens tamoxifen (TAM) and 4-hydroxytamoxifen (OH-TAM) on the induction of two estrogen-specific proteins in a variant of MCF7 cells term...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:A high-affinity localization of [2H]methylcholanthrene and/or its metabolites to a specific nuclear fraction (Fraction l) between 4 and 72 hr of exposure is described. Other carcinogenic hydrocarbons, such as benzo(a)pyrene and dibenz(a,h)anthracene, demonstrate a similar markded localization in Fraction l after 24 hr...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:Drug resistance is a major problem in the successful treatment of cancer. Resistance to one drug is often associated with cross-resistance to other anticancer agents. This is commonly seen with the "natural product" anticancer drugs such as the Vinca alkaloids and anthracyclines. In experimental systems, specific chan...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:The murine monoclonal antibodies TURP-27 and HNK-1 have been shown to detect antigens which are heavily expressed by benign prostatic hyperplasia and carcinoma of the prostate. Western blot analysis of prostate extracts showed that monoclonal antibodies TURP-27 and HNK-1 bound glycoproteins with molecular weights of 1...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation obser...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5-day ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:Cyclin A is an S- and G2-M-phase regulatory protein, and its abnormal expression has been implicated in cellular transformation. This work was undertaken to investigate the frequency of cyclin A overexpression and the correlated clinical outcome in human hepatocellular carcinoma (HCC). Herein, 12 of 31 (39%) patients ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-03-01 00:00:00
abstract：:Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent that appears to form DNA adducts via the reactive pyrazine diazonium ion and produces substantial antitumor activity in preclinical models. We conducted a phase I trial to determine the maximally tolerated dose of PZDH that could be administered as a 5-min...
journal_title：Cancer research
pub_type： 临床试验,杂志文章
doi：
更新日期：1994-01-01 00:00:00
abstract：:Expression of the pro-oncogenic mucin MUC1 is elevated by inflammation in airway epithelial cells, but the contributions of MUC1 to the development of lung cancer are uncertain. In this study, we developed our finding that cigarette smoke increases Muc1 expression in mouse lung macrophages, where we hypothesized MUC1 ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-1713
更新日期：2014-01-15 00:00:00
abstract：:Highly glycolytic cervical cancers largely resist treatment by cisplatin and coadministered pelvic irradiation as the present standard of care. In this study, we investigated the effects of inhibiting glycolysis and thiol redox metabolism to evaluate them as alternate treatment strategies in these cancers. In a panel ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2367
更新日期：2018-03-15 00:00:00
abstract：:Stromal-epithelial interactions and the bioactive molecules produced by these interactions maintain tissue homeostasis and influence carcinogenesis. Bioactive prostaglandins produced by prostaglandin synthases and secreted by the prostate into seminal plasma are thought to support reproduction, but their endogenous ef...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-4439
更新日期：2005-07-15 00:00:00
abstract：:3,3',5-Triiodo-L-thyronine (200 microgram/100 g) is shown to be a potent liver parenchymal cell mitogen in the rat, and thyroidectomy is seen to severely inhibit hepatocyte proliferation in regenerating rat liver. Taken together, these observations point to a crucial role for the iodothyronine in liver cell hyperplasi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
abstract：:We tested the influence of recombinant human interleukin (rhIL)-l3 and rhIL-4 on clonal growth of human breast cancer cell lines. rhIL-13 and rhIL-4 inhibited clonal growth of three of nine lines to approximately 50% of controls (ED50, 0.5 ng/ml). rhIl-13 reduced [3H]thymidine incorporation in all three cell lines: tw...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Previous studies have shown that the invasion of V2 carcinoma cells in the rabbit mesentery is associated with marked extracellular matrix synthesis leading eventually to an overall increase in mesenteric mass. The purpose of the present study was to investigate the structural and biochemical composition of the extrac...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:The s.c.-propagated murine glioma, GL-26, was established in tissue culture. The tissue culture line, with a doubling time of 36 hr, was used as the common source for all tumor cells. Suspensions of the tumor cells were transplanted intracerebrally in mice to produce an anaplastic ependymoblastoma. In vitro 51-Cr cyto...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-03-01 00:00:00
abstract：:Tumor production of parathyroid hormone-related protein (PTHRP) is responsible for most cases of hypercalcemia of malignancy. The transplantable rat Leydig tumor H-500 is known to cause hypercalcemia in rats by the release of abundant PTHRP and to closely reproduce the human syndrome. We have demonstrated recently tha...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-03-15 00:00:00
abstract：:The mechanism of latent membrane protein LMP1 of EBV in inducing cell transformation and tumorigenesis was investigated in Rat-1 fibroblasts. A plasmid encoding a site-specific mutant of LMP1 defective in binding to tumor necrosis factor receptor-associated death domain protein was constructed. This LMP1(TRADD) gene i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-04-01 00:00:00
abstract：:Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified and highly expressed in lobular carcinomas of the breast. In this report, we evaluated the biological activity of FGFR1 in a wide range of in vitro assays. Conditional activation of FGFR1 in the nontransformed MCF10A human mammary cell line, MCF10A, r...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-3398
更新日期：2009-03-15 00:00:00
abstract：:Leucine-rich repeat-containing 3B (LRRC3B) is an evolutionarily highly conserved leucine-rich repeat-containing protein, but its biological significance is unknown. Using restriction landmark genomic scanning and pyrosequencing, we found that the promoter region of LRRC3B was aberrantly methylated in gastric cancer. G...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-0667
更新日期：2008-09-01 00:00:00
abstract：:Cholangiocarcinoma is a strongly aggressive malignancy with a very poor prognosis. Effective therapeutic strategies are lacking because molecular mechanisms regulating cholangiocarcinoma cell growth are unknown. Furthermore, experimental in vivo animal models useful to study the pathophysiologic mechanisms of malignan...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6682
更新日期：2008-08-15 00:00:00
abstract：:An animal lectin purified from loach (Misgurnus anguillicaudatus) eggs induced release of cytotoxin from fresh bone marrow cells from mice, although the other lectins tested, wheat germ agglutinin, concanavalin A, and phytohemagglutinin did not. The cytotoxin released from bone marrow cells was a heat-labile protein w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-01-01 00:00:00
abstract：:Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCCs are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculat...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3121
更新日期：2015-07-15 00:00:00
abstract：:Two sublines, SCLC-MOA1 (MOA1) and SCLC-MOA2 (MOA2), were established from the SCLC-MO cell line, which was originally derived from an oat cell type of small cell lung carcinoma (SCLC). SCLC-MO showed typical culture morphology of SCLC, growing as tightly packed floating aggregates, while both MOA1 and MOA2 grew as a ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:Human papillomavirus (HPV) type 18 DNA was introduced into epithelial cell strains derived from normal and cancer tissues of human prostatectomy specimens by the lipofection transfection method. Two cell lines were established: PZ-HPV-7 (transfected normal cell) and CA-HPV-10 (transfected cancer-derived cell). These l...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
