Abstract:
:Ribonucleotide reductase (RR) is responsible for the de novo conversion of the ribonucleoside diphosphates to deoxyribonucleoside diphosphates, which are essential for DNA synthesis and repair. RR consists of two subunits, hRRM1 and hRRM2. p53R2 is a new RR family member. Because the majority of human tumors possess mutant p53, it is important to know the molecular mechanism by which mutant p53 regulates RR and to what extent. In this study, we investigated the expression and function of p53R2 and hRRM2 after UV treatment in human prostate cancer PC3 cells, which possess mutant p53 with a truncated COOH-terminal, and in human oropharyngeal cancer KB cells, which possess wild-type p53. p53R2 (analyzed by Western blot and standardized relative to Coomassie Blue-stained band) was down-regulated in PC3 cells and up-regulated in KB cells after UV exposure. In contrast, hRRM2 was up-regulated by UV in both PC3 cells and KB cells. hRRM2 and p53R2 mRNA levels were assessed by Northern blot, and the results paralleled that of the Western blot. Coimmunoprecipitation assays using agarose-conjugated goat antihuman RRM1 antibody confirmed that the p53R2 binding to hRRM1 decreased in PC3 cells but increased in KB cells after UV treatment. hRRM2 binding to hRRM1 increased in both cell lines under the same conditions. These results suggest that PC3 cells are deficient in both transcription of p53R2 and binding to hRRM1 in response to UV irradiation. Confocal microscopy further confirmed that these findings were not due to translocation of hRRM2 and p53R2 from the cytoplasm to the nucleus. RR activity was measured following UV treatment and shown to increase in PC3 cells. It was unchanged in proportional of KB cells. The RR activity is consistent with the expression of hRRM2 seen in the Western blots. Thus, we hypothesize that hRRM2 complements p53R2 to form RR holoenzyme and maintain RR activity in PC3 cells after UV treatment. To further confirm this hypothesis, we examined the effect of RRM2 inhibitors on cells exposed to UV. In PC3 cells, hydroxyurea inhibited hRRM2 and resulted in increased sensitivity to UV irradiation. We also examined the effect of UV treatment on the colony-forming ability of cells transfected with hRRM2 as well as p53R2 sense or antisense expression vectors. Expression of antisense hRRM2 in PC3 cells led to decreased hRRM2 expression and resulted in greater sensitivity to UV than observed in wild-type PC3 cells. Taken together, we conclude that UV-induced activation of p53R2 transcription and binding of p53R2 to hRRM1 to form RR holoenzyme are impaired in the p53-mutant cell line PC3.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Zhou B,Liu X,Mo X,Xue L,Darwish D,Qiu W,Shih J,Hwu EB,Luh F,Yen Ysubject
Has Abstractpub_date
2003-10-15 00:00:00pages
6583-94issue
20eissn
0008-5472issn
1538-7445journal_volume
63pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Recently, the cDNA encoding a novel candidate for prostate cancer-specific antigen, named prostate-specific membrane antigen (PSM), was cloned from the LNCaP prostate cancer cell line (R. S. Israeli, C. T. Powell, W. R. Fair, and W. D. W. Heston, Cancer Res., 53: 227-230,1993). More recently, they also identified an a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-06-15 00:00:00
abstract::A synthetic peptide from the inner globule of the B1 chain of laminin, termed peptide F-9 (RYVVLPRPVCFEKGMNYTVR; residues 641-660), has been shown to have heparin-binding and cell adhesion-promoting activities for diverse cell types (Charonis et al., J. Cell. Biol., 107: 1253-1260, 1988). In this study, the metastatic...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-12-01 00:00:00
abstract::Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite mar...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Different cell growth effects were observed in MCF-7 cells after six daily exposures to either 17 beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), or 2-methoxyestradiol (2-MeOE2) at 10 nM levels. 2-OHE2 enhanced cell growth significantly (P < 0.05) more than did the parent compound, whereas 2-MeOE2 inhibited cell gro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::Cancer cell motility has been associated with metastatic potential of sublines of the Dunning R-3227 rat prostatic adenocarcinoma model. However, three sublines of high motility lacked the capacity for metastasis. In all previous works, motility has been studied upon plastic and only upon attached cells at least 18 h ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-12-15 00:00:00
abstract::The spontaneous sister chromatid exchanges (SCEs) and SCEs induced by 50 microM methyl methanesulfonate, 1 microM 4-nitroquinoline 1-oxide, and 5 microM 3-amino-1-methyl-5H-pyrido[4,3-b]indole were examined in phytohemagglutinin-activated peripheral lymphocytes from 53 healthy adult donors. The means of the mean spont...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-01-01 00:00:00
abstract::Plasmacytoid dendritic cells (pDC) are the main producers of a key T-cell-stimulatory cytokine, IFNα, and critical regulators of antiviral immunity. Chronic myeloid leukemia (CML) is caused by BCR-ABL, which is an oncogenic tyrosine kinase that can be effectively inhibited with ABL-selective tyrosine kinase inhibitors...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-1477
更新日期:2018-11-01 00:00:00
abstract::The intranuclear mitosis of the plasmodial nuclei of myxomycetes permits the observation of defects in chromosomal repartition which would probably be lethal in other eukaryotic cells with open mitosis. We found that antitumoral platinum-amine compounds perturbed late mitotic events and induced the formation of giant ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-02-01 00:00:00
abstract::Colorectal cancer cells with stem-like properties, referred to as colon cancer-initiating cells (CCIC), have high tumorigenic potential. While CCIC can differentiate to promote cellular heterogeneity, it remains unclear whether CCIC within a tumor contain distinct subpopulations. Here, we describe the co-existence of ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3198
更新日期:2016-06-01 00:00:00
abstract::Male Wistar rats were given 50 mug of aflatoxin B1 twice a week for 4 weeks, and thereafter 75 mug twice a week for 10 weeks. Their livers were investigated histologically and histochemically for glycogen, RNA, fat, alkaline and acid phosphatases, adenosine triphosphatase, 5'-nucleotidase, glucose-6-phosphatase, gluco...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-10-01 00:00:00
abstract::Although it is widely accepted that tumor suppressor genes play an important role in the genesis and progression of human cancer, little is known about genetic events that accumulate during multistage lung carcinogenesis. Thus, to determine a subset of tumor suppressor genes that are involved in the genesis and progre...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::Traditionally, non-small cell lung cancer (NSCLC) has been evaluated as a unique entity in genotyping studies. However, recent biological data suggest that different NSCLC subtypes, specifically adenocarcinomas (AC) and squamous cell carcinomas (SCC), differentially alter cancer behavior. Several studies have associat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-15 00:00:00
abstract::The rate of repopulation of surviving cells increases during fractionated radiotherapy and limits the ability to control tumors. Repopulation is likely to be more important during the longer intervals between courses of chemotherapy and is a potential cause of clinical resistance to chemotherapy. To evaluate the rate ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Quinocarmycin monicitrate (KW2152) and its analogue, DX-52-1, demonstrated specificity for melanomas in the National Cancer Institute in vitro human tumor cell line drug screen. In contrast to most cell lines, a 50% reduction in tumor cell burden (as measured protein) at the end of a 48-h drug incubation was produced ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-15 00:00:00
abstract::An in vivo model of human CD20+ B-lymphoma was established in severe combined immunodeficiency mice to test the ability of human neutralizing miniantibodies to CD55 and CD59 (MB55 and MB59) to enhance the therapeutic effect of rituximab. The miniantibodies contained single-chain fragment variables and the hinge-CH2-CH...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-1811
更新日期:2007-11-01 00:00:00
abstract::Occurrence of estrone, estradiol, and testosterone glucuronyltranferase activities was tested in a well-differentiated hepatoma, Reuber H35. Transferase activities for estrone and estradiol were found in the hepatoma. The Michaelis-Menten kinetics of these two microsomal glucuronyltransferase activities were similar i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-07-01 00:00:00
abstract::Hepatocellular carcinoma is among the most common and lethal cancers in humans. Hepatocellular carcinoma is commonly associated with physical or functional inactivation of the p53 tumor suppressor, high levels of chromosomal instability, and disease conditions causing chronic cycles of hepatocyte death and regeneratio...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4608
更新日期:2006-05-01 00:00:00
abstract::Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Colony-forming capacity of human melanoma cells was investigated in five established cell lines and isolated cells from seven metastatic or recurrent tumors. A single-cell suspension was added to 0.3% agar medium, and colonies were observed over 7 to 21 days. With the five cell lines, colony formation occurred in all ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00
abstract::Tumor suppressor p53-dependent apoptosis is thought to be one of the most important tumor-suppressive functions in human tumorigenesis. However, whether the major mechanism underlying the p53-dependent apoptosis is transactivation dependent or independent remains unclear. Using 179 mutant p53s with diverse transcripti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-2935
更新日期:2005-03-15 00:00:00
abstract::The human uterine cervix offers a unique opportunity to study the early lesions of squamous cell carcinoma, i.e., carcinoma in situ and dysplasia [combined as cervical intraepithelial neoplasia (CIN)]. In vivo, the patients with CIN have the epidemiological common denominators or "markers" of early onset of coitus, mu...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1976-07-01 00:00:00
abstract::The influence of cyclophosphamide (CY) on Friend virus leukemogenesis was studied in SJL/J, C57BL/10J, and C57BL/10J X SJL/J F1 (hereafter called B10SJF1) mice. All three differ in their susceptibility to the viral oncogenic effect. Immunosuppressive doses of CY, which by themselves produced no cancer, were followed 2...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The administration of 2.5 mg retinyl acetate daily in the diet to female Sprague-Dawley rats beginning 7 days after the intragastric instillation of either 2.5, 5, or 15 mg 7,12-dimethylbenz(a)anthracene (CMBA) resulted in a reduction in the incidence of benign mammary tumors of 37, 30, and 31%, respectively. An equal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-07-01 00:00:00
abstract::Sequence alterations of mitotic checkpoint genes, hBUB1 and hBUBR1, were examined, and their gene transcripts were quantified using on-line, real-time quantitative reverse transcription-PCR in surgically resected human colorectal cancers and their neighboring normal tissues. Our results reveal a new hBUB1 missense mut...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-01 00:00:00
abstract::Myeloproliferative disorders (MPD) are stem cell-derived clonal diseases arising as a consequence of acquired aberrations in c-ABL, Janus-activated kinase 2 (JAK2), and platelet-derived growth factor receptor (PDGFR) that generate oncogenic fusion tyrosine kinases (FTK), including BCR/ABL, TEL/ABL, TEL/JAK2, and TEL/P...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1101
更新日期:2008-09-01 00:00:00
abstract::p53 alterations in human tumors often involve missense mutations that may confer dominant-negative or gain-of-function properties. Dominant-negative effects result in inactivation of wild-type p53 protein in heterozygous mutant cells and as such in a p53 null phenotype. Gain-of-function effects can directly promote tu...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4681
更新日期:2007-05-15 00:00:00
abstract::The flux activities of de novo and salvage purine synthesis were compared in rat hepatoma 3924A cells in various growth phases. The initial rate assays of [14C]adenine, [14C]hypoxanthine, and [14C]guanine incorporation yielded Michaelis-Menten kinetics with Kms of 5, 7, and 7 microM, respectively. After replating plat...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the genetic risk of the majority of breast cancers will require th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-12-15 00:00:00
abstract::10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a week...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Aluminum sulfonated phthalocyanine has potential as a suitable photosensitizer for use in the photodynamic therapy of cancer. In the present study, cellular uptake and retention of the individual mono-, di-, tri-, and tetrasulfonated derivatives (AlS1-4Pc) were examined in tissue culture and in normal and neoplastic t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00