Abstract:
:MYC exerts both positive and negative functions in cancer cells, such that its procancerous effects are unmasked only after its anticancer effects are blocked. Here we used multiple mouse models of lung adenocarcinoma to identify genetic events that can cooperate with MYC activation to promote the genesis of non-small-cell lung cancer (NSCLC), the most common form of lung cancer in humans. MYC overexpression targeted to pulmonary alveolar cells was sufficient to induce lung adenomas and carcinomas. Tumorigenesis was assisted by either spontaneous mutations in Kras or experimental introduction of activated RAS, but investigations revealed that additional events were required to circumvent apoptosis, one of the most significant negative functions exerted by MYC. We determined that overexpression of the antiapoptotic protein MCL1 was sufficient to circumvent apoptosis in this setting. Previous clinical studies have indicated that prognosis of human NSCLC is not associated with MCL1, despite its overexpression in many NSCLCs. In reexamining the prognostic value in this setting, we found that MCL1 overexpression does correlate with poor patient survival, but only when accompanied by MYC overexpression. Our findings therefore produce a convergence of mouse and human results that explain how MCL1 can block an important negative consequence of MYC overexpression in both experimental models and clinical cases of NSCLC.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Allen TD,Zhu CQ,Jones KD,Yanagawa N,Tsao MS,Bishop JMdoi
10.1158/0008-5472.CAN-10-3590subject
Has Abstractpub_date
2011-03-15 00:00:00pages
2212-21issue
6eissn
0008-5472issn
1538-7445pii
71/6/2212journal_volume
71pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Specific pathogen-free cats were immunized with an inactivated feline oncornavirus tumor cell vaccine. Immunized cats produced high antibody titers to the feline oncornavirus-associated cell membrane antigen and were protected from oncogenic feline sarcoma virus challenge. However, immunization did not produce virus-n...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-10-01 00:00:00
abstract::The p75 and p110 isoforms of the CUX1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. To assess and compare the ability of these short CUX1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the Hprt locus to generate transgenic mice expressing p75 or p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4899
更新日期:2009-09-15 00:00:00
abstract::One limitation of autologous bone marrow transplantation for patients with cancer has been the presence of tumor cells in the bone marrow. Methods to eliminate tumor cells while preserving hematopoietic stem cells have been sought. The present study was performed to analyze the in vitro effectiveness of light-activate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::Rational in vivo application of monoclonal antibodies for diagnosis and therapy of cancer requires an understanding of both the global and microscopic pharmacology of macromolecular ligands. Here, we introduce a new mathematical model for antibody distribution into small, prevascular, densely packed nodules (represent...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-09-15 00:00:00
abstract::Iodine-131-labeled anti-CD45 antibody has been added to conventional hematopoietic stem cell transplant preparative regimens to deliver targeted radiation to hematopoietic tissues, with the goal of decreasing relapse rates without increasing toxicity. However, higher radiation doses could be delivered to leukemia cell...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::To reach a clinically detectable size, neoplasms must be able to suppress or evade a host immune response. Activated T cells may enter apoptosis in the presence of Fas ligand (FasL) (1), and tissue expression of FasL has been shown to contribute to immune privilege in the eye and testis (2, 3). We have demonstrated th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-03-15 00:00:00
abstract::The breast- and ovarian-specific tumor suppressor BRCA1 has been implicated in numerous cellular processes, including transcription, ubiquitination, and DNA repair. Its tumor suppression activity is tightly linked to that of BARD1, a protein that heterodimerizes with BRCA1. It has been previously shown that BRCA1 bind...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3296
更新日期:2006-02-15 00:00:00
abstract::The growth and survival of many types of cancer cells are known to be supported by specific growth factor/cytokine systems. Among these, the activation of c-kit receptor and its ligand steel factor participates in several types of human carcinogenesis. W mutations of laboratory mouse strains are loss of functional mut...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Bisphosphonates are widely used clinically to treat bone diseases in which bone resorption is in excess. However, the mechanism of bisphosphonate action on bone is not fully understood. Studies of direct action of bisphosphonates on bone have been limited mainly to their effects on bone-resorbing osteoclast cells, wit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::In the past 3 years, altered expression of the HEF1/CAS-L/NEDD9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. However, whereas some studies have identified elevated NEDD9 expression as prometastatic, other work has suggested a negative role in tumor progression. We here...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0795
更新日期:2009-09-15 00:00:00
abstract::It has been proposed that occult, disseminated metastatic cells are refractory to chemotherapy due to lack of proliferation. We have shown that p38 activation induces dormancy of squamous carcinoma cells. We now show that p38 signaling in these cells activates a prosurvival mechanism via the up-regulation of the endop...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3092
更新日期:2006-02-01 00:00:00
abstract::The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characterist...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0786
更新日期:2008-12-15 00:00:00
abstract::The immune reactivity to partially purified Thomsen-Friedenreich antigen was investigated in patients with lung cancer. The modified method of original leukocyte adherence inhibition test, termed superoxide assay-leukocyte adherence inhibition test, was used to detect the reactivity. The coded peripheral mononuclear c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::In the present study, we examined hemodynamics in vasculogenic mimicry (VM) and angiogenesis of inflammatory breast cancer (IBC) xenografts (WIBC-9), having previously reported on the unique histological features and molecular basis of these processes (K. Shirakawa et al., Cancer Res., 61: 445-451, 2001). Histological...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-01-15 00:00:00
abstract::The transcription factor Dmp1 is a Ras/HER2-activated haplo-insufficient tumor suppressor that activates the Arf/p53 pathway of cell-cycle arrest. Recent evidence suggests that Dmp1 may activate p53 independently of Arf in certain cell types. Here, we report findings supporting this concept with the definition of an A...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-2410
更新日期:2012-04-01 00:00:00
abstract::Crosstalk between tumor and stromal cells in the tumor microenvironment alter its properties in ways that facilitate the invasive behavior of tumor cells. Here, we demonstrate that cancer-associated fibroblasts (CAF) increase the stiffness of the extracellular matrix (ECM) and promote anisotropic fiber orientation, tw...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-1903
更新日期:2015-01-15 00:00:00
abstract::The calcium channel blocker verapamil has been shown to reverse multidrug resistance (T. Tsuruo et al., Cancer Res. 41: 1967-1972, 1981), but the mechanism of action of this agent has not been fully elucidated. A radioactive photoactive analogue of verapamil, N-[benzoyl-3,5-3H-(+/-)-5-[(3,4-dimethoxyphenetyl)methylami...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-15 00:00:00
abstract::Inflammation has increasingly been recognized as a critical component influencing tumor growth. Recent reports have revealed conflicting evidence for the role of Toll-like receptors (TLR) in modulating tumorigenesis. In our study, we implicate TLR3 in mediating immune surveillance with increased growth of implanted tr...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1162
更新日期:2010-04-01 00:00:00
abstract::We have previously reported that several biological agents, when given simultaneously with cytosine arabinoside or cytoxan, will protect from cytosine arabinoside-induced but not from cytoxan-induced alopecia. In the present study we used the secosteroid 1,25-dihydroxyvitamin D3 in a different timing schedule to prote...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-15 00:00:00
abstract::We report the chromosomal characteristics of a recurrent pineal non-seminomatous germ cell tumor in a 16-year-old male patient. This non-seminomatous tumor had the following components: embryonal carcinoma, teratoma, yolk sac tumor, and trophoblastic giant cells. Chromosome analysis showed a near-triploid karyotype (6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-03-15 00:00:00
abstract::A widely held tenet of present day oncology is that tumor cells treated with anticancer agents die from apoptosis, and that cells resistant to apoptosis are resistant to cancer treatment. We suggest, in this review, that this tenet may need to be reexamined for human tumors of nonhematological origin, for two principa...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1999-04-01 00:00:00
abstract::Breast cancer-initiating cells have been recently identified in breast carcinoma as CD44+/CD24(-/low) cells, which exclusively retain tumorigenic activity and display stem cell-like properties. However, at present, direct evidence that breast cancer-initiating cells can be propagated in vitro is still lacking. We repo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0626
更新日期:2005-07-01 00:00:00
abstract::We have used a transplantable experimental murine renal carcinoma (Renca) to evaluate the adjuvant immunotherapeutic potential of cytotoxic lymphocytes stimulated by in vitro incubation for 24 h with human recombinant interleukin 2 (rIL-2). The Renca tumor model is therapeutically challenging since, following intraren...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Several reports have suggested that a decrease or absence of adenosine deaminase complexing protein (ADCP) is consistently associated with cancer. However, in other studies, decreased as well as increased ADCP levels were found. In the present study, we investigated ADCP levels in 37 colorectal adenocarcinomas and cor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-10-01 00:00:00
abstract::Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4350
更新日期:2007-05-01 00:00:00
abstract::Chronic exposure to the hepatocellular carcinogen diethylnitrosamine (DEN) causes a dose-dependent accumulation of the promutagenic DNA adduct O4-ethyldeoxythymidine in hepatocytes and increases in the number of initiated hepatocytes as indicated by gamma-glutamyl transpeptidase positive foci. Initiation is thought to...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-15 00:00:00
abstract::N-4-Hydroxyphenylretinamide (fenretinide or 4HPR), a derivative of retinoic acid, has been demonstrated to decrease the development of prostate cancer in a rat carcinogenesis model. This study was undertaken to determine if 4HPR is an effective agent for the treatment of established prostate cancer. In vitro, 4HPR was...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-01-15 00:00:00
abstract::Radiolabeled antibodies have produced encouraging remissions in patients with chemotherapy-resistant hematological malignancies; however, the selection of therapeutic radionuclides for clinical trials remains controversial. In this study, we compared the internalization, lysosomal targeting, metabolism, and cellular r...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::Frequent loss of heterozygosity (LOH) on the long arm of chromosome 5 (5q) has been reported in many types of human malignancies, including gastric carcinoma. One of the targets of 5q-LOH in colorectal carcinoma is certainly the adenomatous polyposis coli (APC) gene on 5q21. However, other evidence has suggested the p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Physical activity is defined as bodily movement due to skeletal muscle contraction that results in quantifiable energy expenditure. Both epidemiological and laboratory data indicate that the level of physical activity in which an individual engages may affect cancer risk. Exercise is distinguished from other types of ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1994-04-01 00:00:00