Abstract:
:Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens. Hypersensitivity of beta-pol-deficient cells to methylating agents is because of induction of apoptosis (Ochs et al., Cancer Res., 59: 1544-1551, 1999), indicating incompletely repaired DNA damage to trigger the response. Here we show that defective BER in beta-pol-null cells results in an early and transient increase in the frequency of DNA single-strand breaks on treatment with methyl methanesulfonate. These breaks arising as repair intermediates are not likely to trigger apoptosis directly because they were repaired efficiently and generated both in resting and proliferating cells, whereas only proliferating cells underwent with high frequency apoptosis after methylation. Therefore, we propose that single-strand breaks are converted into another kind of critical apoptosis-triggering lesion during replication. These critical secondary DNA lesions are likely to be non-repaired DNA double-strand breaks (DSBs), which are formed at higher frequency in beta-pol-null than in wild-type cells. Apoptosis was a late response not detectable before 24 h after methylation and was preceded by DSBs formation, extensive chromosomal breakage, and decline in Bcl-2 level and caspase-9 and caspase-3 activation. Caspase-8 was not significantly activated. Transfection of beta-pol-null cells with bcl-2 protected against methylation-induced apoptosis, indicating Bcl-2 to be causally involved. Overall, the data demonstrate that in cells lacking beta-pol, defective BER results in incompletely repaired DNA damage, which triggers apoptosis in a replication-dependent way by activating the mitochondrial death pathway. It is suggested that DSBs act as a critical ultimate apoptosis-inducing lesion.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Ochs K,Lips J,Profittlich S,Kaina Bsubject
Has Abstractpub_date
2002-03-01 00:00:00pages
1524-30issue
5eissn
0008-5472issn
1538-7445journal_volume
62pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Postpartum mammary gland involution is a tissue remodeling event that occurs in all mammals in the absence of nursing or after weaning to return the gland to the pre-pregnant state. The tissue microenvironment created by involution has proven to be tumor promotional. Here we report that the GPI-linked protein semaphor...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-1642
更新日期:2018-11-15 00:00:00
abstract::Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-01 00:00:00
abstract::Sphingosine-1-phosphate is a potent lipid mediator formed by phosphorylation of sphingosine, a metabolite of sphingolipids, catalyzed by two sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2. Expression of SphK2, which is enriched in the nucleus of MCF7 human breast cancer cells, increased expression of the cyclin...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2090
更新日期:2007-11-01 00:00:00
abstract::The MAGE-1 gene codes for a tumor-specific antigen, MZ2-E, that elicited a cytotoxic T-lymphocyte response in the melanoma patient from whom it was derived. We have developed a simplified method, using polymerase chain reaction amplification of exon 3 followed by restriction enzyme pattern analysis, to distinguish exp...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Cetuximab, the FDA-approved anti-EGFR antibody for head and neck squamous cell carcinoma (HNSCC), has displayed limited efficacy due to the emergence of intrinsic and acquired resistance. We and others have demonstrated that cetuximab resistance in HNSCC is driven by alternative receptor tyrosine kinases (RTK), includ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0459
更新日期:2018-08-01 00:00:00
abstract::nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Malignant undifferentiated sarcomas were induced in 11 of 15 (73.3%) newborn Syrian hamsters by s.c. inoculation of a recombinant DNA (pBK/c-rasA) containing BK virus (BKV) early region gene and the activated human c-Harvey-ras(c-Ha-ras) oncogene derived from T24 bladder carcinoma. The two genes inoculated independent...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-15 00:00:00
abstract::Embryonal carcinoma cells localize to a specific array of target tissues including the male submaxillary gland following intracardiac injection. These target tissues or conditioned medium derived from them have been shown to stimulate the in vitro migration of embryonal carcinoma cells. Here we show that in vitro migr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Cigarette smoke contains low levels of agonists for the aryl hydrocarbon receptor (AhR; also called the dioxin receptor). However, little is understood about the whole potential of cigarette smoke for activating AhR. In this report, we evaluated the total "dioxin-like" activity of cigarette smoke using in vitro and in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-4541
更新日期:2006-07-15 00:00:00
abstract::Transplabtable Zajdela rat ascites hepatoma cells, previously considered "nonproducers," synthesize detectable amounts of intracellular alpha-fetoprotein (AFP) and fibrinogen, but fail to secret or release these serum proteins. Evidence for defective secretory mechanisms for serum proteins in these hepatoma cells (a) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::Cancer is a leading cause of mortality throughout the world and new treatments are urgently needed. Recent studies suggest that bone marrow-derived mesenchymal stem cells (MSC) home to and incorporate within tumor tissue. We hypothesized that MSCs engineered to produce and deliver tumor necrosis factor-related apoptos...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4698
更新日期:2009-05-15 00:00:00
abstract::The chemotherapeutic agent 6-mercaptopurine was previously shown to inhibit the binding of 7r,8t-dihydroxy-9,10t-oxy-7,8,9,10-tetrahydro-benzo(a) pyrene (BPDE-I) to DNA in Chinese hamster ovary cells. Two compounds related to 6-mercaptopurine, 2,6-dithiopurine (DTP) and thiopurinol (TP), have been tested for inhibitio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-09-15 00:00:00
abstract::Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) are rare genodermatoses transmitted as recessive and autosomal traits that result in reduced capacity to repair UV-induced DNA lesions. Although XP, but not TTD, patients are prone to basal and squamous cell carcinomas, to date no comparative studies of the XP a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-03-15 00:00:00
abstract::Carcinoembryonic antigen (CEA) is a glycoprotein metabolized primarily by the liver. Subcellular fractions of rat liver were examined for CEA binding activity. Hepatocyte plasma membrane and microsome fractions bound CEA, and this binding shared the calcium requirement, neuraminidase sensitivity, and carbohydrate spec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-07-01 00:00:00
abstract::I have attempted to illustrate the many different properties of retroviruses and their presence in a wide variety of animal species including humans. Since the turn of this century, progress in the field of retrovirology has been noteworthy and many new and important scientific observations have been made (Table 7). A...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1986-11-01 00:00:00
abstract::Noscapine, a benzylisoquinoline alkaloid derived from opium, was recently reported to exhibit activity against a variety of cancers through a poorly understood mechanism. Because the transcription factor NF-kappaB has been linked with inflammation, survival, proliferation, invasion, and angiogenesis in tumors, we hypo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4230
更新日期:2010-04-15 00:00:00
abstract::The expression of genes which may be involved in the regulation of human mammary epithelial cell growth [transforming growth factors alpha and beta] and tumorigenesis [c-myc, erbB2, epidermal growth factor receptor (EGFR), Ha-ras, pS2] has been compared in similarly cultured normal cell strains and tumor cell lines. W...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-12-15 00:00:00
abstract::SGN-40 is a humanized IgG1 antihuman CD40 that is currently in a phase I clinical trial for the treatment of multiple myeloma. As surface CD40 expression on B-lineage cells is maintained from pro-B cells to plasma cells, SGN-40 may be applicable to treatment of other B-cell neoplasias, including non-Hodgkin's lymphoma...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0095
更新日期:2005-09-15 00:00:00
abstract::Delivery of therapeutic agents to the brain and its neoplasms depends on the presence of membrane transport proteins in the blood-brain barrier and in the target cells. The cellular and subcellular localization of these membrane transporters determines the drug accessibility to the brain and its tumors. We therefore a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1271
更新日期:2005-12-15 00:00:00
abstract::Uptake of actinomycin D (AD) was characterized in Ehrlich ascites tumor cells in vitro. The time course of uptake consists of an initial component that represents a unidirectional flux of AD into the cells, following which the net uptake rate falls to achieve a velocity that is constant over a 45-min interval of obser...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-11-01 00:00:00
abstract::Despite studies that show the antitumor activity of Hsp90 inhibitors, such as geldanamycin (GA) and its derivative 17-allylamino-demethoxygeldanamycin (17-AAG), recent reports indicate that these inhibitors lack significant single-agent clinical activity. Resistance to Hsp90 inhibitors has been previously linked to ex...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5175
更新日期:2008-09-15 00:00:00
abstract::Hypoxia inducible factors (HIF) are critical mediators of the cellular response to decreased oxygen tension and are overexpressed in a number of tumors. Although HIF1alpha and HIF2alpha share a high degree of sequence homology, recent work has shown that the two alpha subunits can have contrasting and tissue-specific ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4223
更新日期:2009-04-01 00:00:00
abstract::Epithelial-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is considered a key process driving tumor cell invasiveness and metastasis. Using breast cancer cell lines as a model system, we sought to discover gene expression signatures of EMT with clinical an...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-3141
更新日期:2010-03-15 00:00:00
abstract::Therapeutic inhibition of mammalian target of rapamycin (mTOR) in cancer is complicated by the existence of a negative feedback loop linking mTOR to the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Thus, mTOR inhibition by rapamycin or TSC1/2 results in increased PI3K-Akt activation. The death domain kinase recep...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0474
更新日期:2009-05-15 00:00:00
abstract::Rats were fed sodium saccharin as 5 or 7.5% of the diet by weight, and proliferation of the bladder epithelium was assessed by autoradiography, histology, and scanning electron microscopy. In Experiment 1, male F344 rats, 5 weeks old, were placed on a diet of 0, 5, or 7.5% NaS mixed in Prolab 3200, NIH-07, or AIN-76A ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-07-15 00:00:00
abstract::The tumor suppressor phosphatase and tensin homologue (PTEN) is involved in cell proliferation, adhesion, and apoptosis. PTEN overexpression in mammary epithelium leads to reduced cell number and impaired differentiation and secretion. In contrast, overexpression of the proto-oncogene Wnt-1 in mammary epithelium leads...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0181
更新日期:2005-08-01 00:00:00
abstract::Dendritic cells (DCs) are professional antigen-presenting cells, well equipped to initiate an immune response. Currently, tumor antigen-derived peptide loaded DCs are used in clinical vaccination in cancer patients. However, the optimal dose and route of administration of a DC vaccine still remain to be determined. Us...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::Prostate cancer biology varies from locally confined tumors with low risk for relapse to tumors with high risk for progression even after radical prostatectomy. Currently, there are no reliable biomarkers to predict tumor relapse and poor clinical outcome. In this study, we correlated expression patterns of the androg...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1570
更新日期:2006-12-01 00:00:00
abstract::The cyanomorpholino derivative of doxorubicin (MRA-CN) is a DNA intercalator and alkylator that is a highly potent cytotoxin, non-cross-resistant in multidrug-resistant cells, and noncardiotoxic in comparison with doxorubicin. To further examine mechanisms of action and resistance to MRA-CN, a cell line resistant to M...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Galectin-3, a beta-galactoside binding protein, plays a significant role in cell to extracellular matrix interactions. Despite its extracellular expression, the precise physiological mechanisms that trigger its release from the intracellular milieu have not been characterized. The present analyses were, therefore, don...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00