Abstract:
:ERBB4/HER4 (referred to here as ERBB4) is a unique member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. In contrast to the other three members of the EGFR family (i.e., EGFR, ERBB2/HER2/NEU, and ERBB3), which are associated with aggressive forms of human cancers, ERBB4 expression seems to be selectively lost in tumors with aggressive phenotypes. Consistent with this observation, we show that ERBB4 induces apoptosis when reintroduced into breast cancer cell lines or when endogenous ERBB4 is activated by a ligand. We further show that ligand activation and subsequent proteolytic processing of endogenous ERBB4 results in mitochondrial accumulation of the ERBB4 intracellular domain (4ICD) and cytochrome c efflux, the essential and committed step of mitochondrial regulated apoptosis. Our results indicate that 4ICD is functionally similar to BH3-only proteins, proapoptotic members of the BCL-2 family required for initiation of mitochondrial dysfunction through activation of the proapoptotic multi-BH domain proteins BAX/BAK. Similar to other BH3-only proteins, 4ICD cell-killing activity requires an intact BH3 domain and 4ICD interaction with the antiapoptotic protein BCL-2, suppressed 4ICD-induced apoptosis. Unique among BH3-only proteins, however, is the essential requirement of BAK but not BAX to transmit the 4ICD apoptotic signal. Clinically, cytosolic but not membrane ERBB4/4ICD expression in primary human breast tumors was associated with tumor apoptosis, providing a mechanistic explanation for the loss of ERBB4 expression during tumor progression. Thus, we propose that ligand-induced mitochondrial accumulation of 4ICD represents a unique mechanism of action for transmembrane receptors, directly coupling a cell surface signal to the tumor cell mitochondrial apoptotic pathway.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Naresh A,Long W,Vidal GA,Wimley WC,Marrero L,Sartor CI,Tovey S,Cooke TG,Bartlett JM,Jones FEdoi
10.1158/0008-5472.CAN-05-2368subject
Has Abstractpub_date
2006-06-15 00:00:00pages
6412-20issue
12eissn
0008-5472issn
1538-7445pii
66/12/6412journal_volume
66pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::We previously reported that thymidine kinase (TK) activity in a spontaneously TK-deficient (TK-) mouse tumor cell line (called L61-M) could be partially restored by brief exposure of the cells in vitro to the DNA-hypomethylating agent 5-azacytidine. We now show that similar results can be obtained by exposing L61-M ce...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-11-01 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::The association of intrauterine exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities in young women has been well documented. Although the incidence of vaginal adenocarcinoma was low in the exposed population, vaginal adenosis, a nonmalignant abnormality, was quite co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::An immunogenic tumor and a nonimmunogenic tumor were used in C57BL/Ka and CBA/Rij mice, respectively, in a study in which lymph node morphology was quantitatively measured. Lymph nodes were cut in semiseries, and a morphometrical analysis was done on the paracortical and cortical areas as major parts of the active lym...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-03-01 00:00:00
abstract::We have cloned a gene, BDP, encoding a protein with homology to the retinoblastoma-binding proteins Rbp1 and Rbp2. It also has homology to DNA-binding proteins such as Bright, a B-cell-specific trans-activator, and the Drosophila melanogaster dead ringer gene product. Like MyoD, Bdp binds to the COOH-terminal region o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-08-01 00:00:00
abstract::Breast cancer stem-like cells (BCSC) have been implicated in tumor growth, metastasis, drug resistance, and relapse but druggable targets in appropriate subsets of this cell population have yet to be identified. Here we identify a fundamental role for the prolyl isomerase Pin1 in driving BCSC expansion, invasiveness, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-2785
更新日期:2014-07-01 00:00:00
abstract::In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lym...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-2968
更新日期:2004-03-01 00:00:00
abstract::Identification of proteins that are involved in the sensitivity of radiotherapy of cancers is important to enhance the response to cancer treatment. Expression of TAp73 is associated with the sensitivity of radiotherapy in cervical cancer patients, suggesting it plays an important role in controlling radiosensitivity....
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0688
更新日期:2010-08-15 00:00:00
abstract::RS7, a murine IgG1 antibody raised against human lung carcinoma, possesses pancarcinoma reactivity. The antigen defined by this antibody is present in tumors of the lung, stomach, bladder, breast, ovary, uterus, and prostate. Efficient targeting and therapy by radiolabeled RS7 has been demonstrated previously in anima...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines der...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-2687
更新日期:2009-12-01 00:00:00
abstract::Cloning efficiencies of 67 fresh human tumor specimens, consisting of 29 ovarian, 10 lung, and 7 each of colon, breast, mesenchymal, and miscellaneous tumors, from 58 patients were studied using the technique of Hamburger and Salmon to evaluate the effect of incubation in a 5% rather than 20% oxygen environment. Under...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00
abstract::Sleep fragmentation (SF) is a highly prevalent condition and a hallmark of sleep apnea, a condition that has been associated with increased cancer incidence and mortality. In this study, we examined the hypothesis that sleep fragmentation promotes tumor growth and progression through proinflammatory TLR4 signaling. In...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-3014
更新日期:2014-03-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy typified by a highly stromal and weakly immunogenic tumor microenvironment that promotes tumor evolution and contributes to therapeutic resistance. Here, we demonstrate that PDA tumor cell-derived proinflammatory cytokine IL1β is essential for the esta...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-2080
更新日期:2020-03-01 00:00:00
abstract::The translation initiation factor eIF4E is an oncogene that is commonly overexpressed in primary breast cancers and metastases. In this article, we report that a pharmacologic inhibitor of eIF4E function, ribavirin, safely and potently suppresses breast tumor formation. Ribavirin administration blocked the growth of p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-1996
更新日期:2015-03-15 00:00:00
abstract::Growth factors play an important role in regulating neural stem cell proliferation and differentiation. This study shows that platelet-derived growth factor (PDGF) induces a partial differentiation of neural stem/progenitor cells (NSPCs) in the absence of other mitogens in vitro. NSPCs thus acquire an immature morphol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-0900
更新日期:2006-08-15 00:00:00
abstract::Mitogen-activated protein kinase (MAPK) is activated in the majority of melanomas, and its activity is essential for cell survival. In this report, we examined the effects of a novel raf inhibitor BAY 43-9006 on melanoma cell viability and intracellular signaling and found that it induces apoptosis through a caspase-i...
journal_title:Cancer research
pub_type: 杂志文章,收录出版
doi:10.1158/0008-5472.CAN-05-0808
更新日期:2006-02-01 00:00:00
abstract::We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus receptor) as a regulator of cancer invasiveness and glioma migration, but the mechanism through which CD155/PVR controls these processes is unknown. Here, we show that expression of CD155/PVR in rat glioma cells that normally lack this protein enh...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1890
更新日期:2005-12-01 00:00:00
abstract::Nile blue derivatives have been shown to be potentially effective photosensitizers for photodynamic therapy of malignant tumors. Results of a previous study suggested that the high accumulation of these dyes in cells may be the result of dye aggregation, partition in membrane lipids, and/or sequestration in subcellula...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::Myc oncoproteins exert tumorigenic effects by regulating expression of target oncogenes. Histone H3 lysine 79 (H3K79) methylation at Myc-responsive elements of target gene promoters is a strict prerequisite for Myc-induced transcriptional activation, and DOT1L is the only known histone methyltransferase that catalyzes...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1663
更新日期:2017-05-01 00:00:00
abstract::Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient cha...
journal_title:Cancer research
pub_type: 杂志文章,多中心研究
doi:10.1158/0008-5472.CAN-19-1554
更新日期:2019-10-15 00:00:00
abstract::Ionizing radiation is a major tool for cancer treatment. The response of eukaryotic cells to ionizing radiation includes apoptosis, a process which requires activation of multiple genes. We sought to determine whether radiation-induced gene expression plays a role in radiation-induced apoptosis. We found Apo2 ligand (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-10-15 00:00:00
abstract::Human malignant mesothelioma of the pleura was successfully transplanted s.c. into athymic nude mice and grew as a solid neoplastic mass. Tumor growth resulted in death of the animals between 98 and 161 days after implantation. Minced samples of the growing tumor were propagated as a malignant peritoneal effusion. Ani...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-15 00:00:00
abstract::Prostate-specific membrane antigen (PSMA), initially defined by monoclonal antibody (mAb) 7E11, is a now well-characterized type 2 integral membrane glycoprotein expressed in a highly restricted manner by prostate epithelial cells. 7E11 has been shown to bind an intracellular epitope of PSMA that, in viable cells, is ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-09-01 00:00:00
abstract::The activity of the serine protease plasminogen activator (PA), which correlates with tumorigenicity and metastatic capacity, was examined using the 125I-labeled fibrin plate assay in cell extracts from four human glioma lines as a function of growth in vitro. Cell-associated inhibitory activity to plasmin and urokina...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-01-15 00:00:00
abstract::Disease recurrence and metastasis are frequently observed in many successfullytreated localized cancers, including hepatocellular carcinoma in which intrahepatic and extrahepatic recurrence (metastasis) are frequently observed after curative resection. The present study aimed at identifying metastasis-associated genes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::We reported previously that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, markedly enhanced methylcholanthrene-induced transformation of BALB 3T3 A31-1-1 cells. When the cells were treated with methylcholanthrene (1 microgram/ml) for 72 h and then with 1 alpha,25(OH)2D3 (5...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-02-01 00:00:00
abstract::The cell surface molecules controlling apoptosis in cortical neurons are largely unknown. A monoclonal antibody was derived that induces cultured neocortical neurons to undergo apoptosis. A Fab fragment of the antibody, however, lacked the ability to induce cell death. The antigen was purified, and characterized by co...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::In 1984, we reported that while immunoreactive levels of serum alpha-1 proteinase inhibitor (API) increased significantly in nine patients with advanced solid tumors, the functional activity of the inhibitor, as measured by the serum trypsin inhibitory capacity, did not increase proportionately. This suggested that a ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-02-15 00:00:00
abstract::There is widespread agreement that cancer gene discovery requires high-quality tumor samples. However, whether primary tumors or cultured samples are superior for cancer genomics has been a longstanding subject of debate. This debate has recently become more important because federally funded cancer genomics has been ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1055
更新日期:2009-07-15 00:00:00