Abstract：
:The ability of cancer cells to evade apoptosis is dictated by a shift in the balance between proapoptotic and antiapoptotic gene expression programs. Monocyte chemotactic protein-induced protein 1 (MCPIP1) is a zinc-finger RNA binding protein with important roles in mediating inflammatory responses. Overexpression of MCPIP1 in different cancer cell types has been implicated in eliciting an antitumor response, but a direct role of MCPIP1 in apoptosis has not been established. In this study, we demonstrate that MCPIP1 functions as a potent tumor suppressor that induces apoptosis of breast tumor cells by selectively enhancing mRNA decay of antiapoptotic gene transcripts, including Bcl2L1, Bcl2A1, RelB, Birc3, and Bcl3. Mechanistically, MCPIP1 physically interacted with a stem-loop structure in the 3' untranslated region of these transcripts through its PIN domain, causing mRNA destabilization. Furthermore, we found that MCPIP1 expression was repressed in breast tumor cells, and overexpression of MCPIP1 induced apoptosis, whereas its depletion enhanced cancer cell proliferation. Moreover, MCPIP1 induction in vivo resulted in complete regression of established tumors and a significant reduction in metastatic disease. Notably, low MCPIP1 expression in tumor samples from breast cancer patients was strongly associated with poor survival over 13 years of follow-up. Collectively, our results highlight that MCPIP1 is a new tumor suppressor in breast cancer that induces cell death by tipping the balance in favor of proapoptotic gene expression.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Lu W,Ning H,Gu L,Peng H,Wang Q,Hou R,Fu M,Hoft DF,Liu Jdoi
10.1158/0008-5472.CAN-15-1115subject
Has Abstractpub_date
2016-03-15 00:00:00pages
1429-40issue
6eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-1115journal_volume
76pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Elimination of both alleles of the gene that encodes the cyclin kinase inhibitor p21(WAF1/cip1) increases the frequency and size of intestinal tumors in Apc1638+/- mice that inherit a mutant allele of the Apc gene, and intermediate effects are seen if a single p21 allele is inactivated. The increased tumor formation i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-15 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：:The human nm23 gene, a candidate metastatic suppressor gene, consists of two genes, nm23-H1 and nm23-H2. The potential mutation in the nm23-H1 gene was examined in colorectal cancer using a reverse transcription polymerase chain reaction amplification followed by DNA sequencing analysis. Genomic alterations in the nm2...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-02-15 00:00:00
abstract：:Amino acid analysis of the culture medium was carried out in a human leukemic lymphoblastoid cell line (REH) established from the lymphoblasts of a patient with acute lymphoid leukemia. The results are compared with those of a reference cell line (LHN13) established from normal human lymphocytes. The most striking dif...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-11-01 00:00:00
abstract：:DNA polymerase beta is a nuclear protein essential to DNA repair in mammalian cells. A high frequency of mutations in this gene has been reported in colorectal cancers. To clarify the tumorigenesis steps of human prostate cancers in the molecular basis, we examined the entire coding region of the human DNA polymerase ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-06-01 00:00:00
abstract：:Sixteen clones (RASK-1 to -16) of murine monoclonal antibodies were raised against ras Mr 21,000 protein (p21). The p21 produced by Escherichia coli with inserted v-Ki-ras genes was used as immunogen. RASK-1 was found to be specific for Ki-ras p21, whereas RASK-2 to -16 reacted with the p21s of Ki-, N-, and Ha-ras gen...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:The role of oxygen free radicals in the toxicity and antitumor effect of tumor necrosis factor was investigated in vivo. Treatment of non-tumor-bearing mice and mice bearing methylcholanthrene-induced sarcomas with bovine CuZn superoxide dismutase or recombinant human CuZn superoxide dismutase afforded significant pro...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-15 00:00:00
abstract：:Osteosarcoma is the most common malignant bone tumor in children. Osteosarcoma patients who respond poorly to chemotherapy are at a higher risk of relapse and adverse outcome. Therefore, it was the aim of this study to identify prognostic factors at the time of diagnosis to characterize the genes predictive of poor su...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2463
更新日期：2005-03-01 00:00:00
abstract：:Using a microcytotoxicity assay we have studied the immune responses to the preneoplastic, hyperplastic alveolar nodule (HAN) lines D1 and D2 and to the mammary tumors arising spontaneously from them in BALB/c mice. Lymph node cells (LNC) from mice bearing HAN implants, or from mice whose implants had been removed gre...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-02-01 00:00:00
abstract：:The interaction of the activating receptor NKG2D with its ligands plays an important role in immunosurveillance of tumors and infectious pathogens, but dysregulation of this system may lead to autoimmunity. The expression of NKG2D ligands is induced by cellular "stress." However, the regulation of expression of these ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2973
更新日期：2008-03-01 00:00:00
abstract：:1-Nitropyrene, a direct-acting mutagenic component of extracts of diesel exhaust and ambient air particulates, is one of the major nitroarenes found in products of incomplete combustion. Injection of this compound into newborn Sprague-Dawley-derived CD rats at 100 mumol/kg body weight s.c. once a week for 8 weeks indu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
abstract：:Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the re...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3534
更新日期：2015-06-15 00:00:00
abstract：:Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins. The MKK4 protein has been implicated in activation of JNK1 and p38 MAPK on phosphorylation by conserved kinase pathways. A recent report on the deletion and mutat...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-10-15 00:00:00
abstract：:Non-small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed "stromal cells") that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenv...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-1529
更新日期：2008-09-01 00:00:00
abstract：:It has been well established that overexpression of Cyclooxygenase-2 (Cox-2) in epithelial cells inhibits apoptosis and increases the invasiveness of malignant cells, favoring tumorigenesis and metastasis. However, the molecular mechanism that regulates Cox-2 expression has not been well defined in gastric carcinoma. ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-06-01 00:00:00
abstract：:This study investigates whether and to what extent cyclooxygenase type-2 (COX-2) and inducible nitric oxide-synthase (iNOS), both known to have an immunosuppressive effect, are expressed in human ovarian tumors. Because COX-2 and iNOS can be expressed by activated macrophages, the presence of tumor-associated macropha...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:Myeloma vaccines, based on dendritic cells pulsed with idiotype or tumor lysate, have been met with limited success, probably in part due to insufficient cross-priming of myeloma antigens. A powerful method to introduce myeloma-associated antigens into the cytosol of dendritic cells is protein transduction, a process ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1383
更新日期：2005-11-01 00:00:00
abstract：:Phenotypic variability of the human neuroblastoma cell line SK-N-SH was studied with the use of three subclones that interconvert at a slower rate than the parent cell line, i.e., a neuroblast-type subclone (SH-SY5Y), a nonneuronal, strongly substrate adherent subclone (SH-EP), and an intermediate type subclone (SH-IN...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:The biochemical and clinical effects of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats are presented. A 4-ppm selenium supplement to the drinking water was provided before, during, and after 20 weekly injections of 20 mg DMH per kg body weight. Immediately af...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:This study investigated the ultrastructure and development of virus particles detected in a spontaneous mammary tumor of an 8 year old rhesus monkey. During a 3-month period of tumor growth, several biopsies were performed. Thin section electron microscopy of the tumor tissue revealed 2 types of particles: 1) an in...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1970-08-01 00:00:00
abstract：:We previously reported that amino acids 20 to 50 of nuclear receptor interacting factor-3 mediates rapid apoptosis in breast cancer cell lines but not in cells derived from other tissues. We refer to this short region as death domain-1 (DD1). Small interfering RNA studies indicated that DD1-mediated apoptosis is caspa...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-4034
更新日期：2007-02-15 00:00:00
abstract：:Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rs1447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Can...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-3591
更新日期：2007-04-01 00:00:00
abstract：:Approximately 10% of gastric adenocarcinomas worldwide are associated with human EBV. These carcinomas generally do not express the latent membrane protein 1 (LMP1), the major known EBV oncogene. Recently, another EBV gene [ie., BARF1 (BamHI A rightward open reading frame)] was shown to have transforming and immortali...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-05-15 00:00:00
abstract：:Epithelial-mesenchymal transition (EMT) is a developmental program, which is associated with breast cancer progression and metastasis. Here, we report that ectopic overexpression of SOX4 in immortalized human mammary epithelial cells is sufficient for acquisition of mesenchymal traits, enhanced cell migration, and inv...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-12-1045
更新日期：2012-09-01 00:00:00
abstract：:Ovarian and testicular tumors were induced in the offspring (F1 generation) of MRC rats that received single or multiple doses of N-nitrosobis(2-oxopropyl)amine on the 14th, 18th, and/or 20th days of pregnancy. The ovarian tumor incidence was significantly higher (46%) in the F1 generation exposed to the carcinogen a ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:The prostate-specific antigen (PSA) promoter (PSA-P) has been identified, characterized, and determined to be tissue specific. Compared with high expression of the genomic PSA gene in prostate cells, expression of the transgene driven by the putative PSA promoter is low. This suggests that the identified promoter may ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:Alkaline phosphatase was extracted from human gastric carcinoma cells (KMK-2) under long-term culture, and its biochemical and biological properties were investigated. The enzyme was extremely heat labile and was inhibited significantly by L-homoarginine, but only slightly by L-phenylalanine, so that it was classified...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-11-01 00:00:00
abstract：:Hypoxia within solid tumors decreases therapeutic efficacy, and identification of hypoxia markers may influence the choice of therapeutic modality. Here, we used a proteomic approach to identify hypoxia-regulated proteins and validated their use as endogenous indicators of tumor hypoxia. Using two-dimensional gel elec...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-0899
更新日期：2004-10-15 00:00:00
abstract：:The rapidly expanding understanding of the progressive processes of carcinogenesis provides opportunities for the identification of molecular biological markers reflecting events from exposure through clinical disease. These molecular biological markers can be classified into categories of markers of exposure reflecti...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：
更新日期：1994-04-01 00:00:00
