Abstract：
:PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated in both primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-ras(G12D/WT) mice with the prostate conditional Pten deletion model. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penetrance. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a mitogen-activated protein (MAP)-extracellular signal-regulated (ER) kinase (MEK) inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, our findings indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis, and cotargeting both the pathways is highly effective in preventing the development of metastatic prostate cancers.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mulholland DJ,Kobayashi N,Ruscetti M,Zhi A,Tran LM,Huang J,Gleave M,Wu Hdoi
10.1158/0008-5472.CAN-11-3132subject
Has Abstractpub_date
2012-04-01 00:00:00pages
1878-89issue
7eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-11-3132journal_volume
72pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:The role of the NKG2D immunoreceptor and its ligands in antitumor immune response is incompletely understood. Here, we report that effector immune cells infiltrating ovarian carcinoma are mostly CD8+ lymphocytes lacking CD28 but expressing the NKG2D costimulatory receptor. Human ovarian carcinoma expresses the novel N...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-2194
更新日期：2004-03-15 00:00:00
abstract：:Protection of spermatogenesis from cytotoxic drug-induced damage has been investigated in the rat. Complete germinal aplasia was observed at 8 and 11 weeks after four doses of procarbazine hydrochloride administered weekly (150 mg/kg, first dose; 100 mg/kg, 3 subsequent doses). Pretreatment of rats for 6 weeks plus co...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-04-01 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：:That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neurobl...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:The hyperthermic sensitivity of cultured human glioblastoma cells was determined in 1 degree increments from 42 through 46 degrees over the pH range of 6.1 to 7.4. These cells were 5 to 10 times less heat sensitive than were Chinese hamster ovary cells and are among the most resistant cells examined in cell culture. A...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-03-01 00:00:00
abstract：:Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are lysophospholipid mediators of diverse cellular processes important for cancer progression. S1P is produced by two sphingosine kinases, SphK1 and SphK2. Expression of SphK1 is elevated in many cancers. Here, we report that LPA markedly enhanced SphK1 mRN...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-0411
更新日期：2008-08-15 00:00:00
abstract：:Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G2-M consistent with its known effects on the mitotic spindle and potentially could be ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-03-15 00:00:00
abstract：:A series of rat 13762NF mammary adenocarcinoma cell clones and subclones of various lung metastatic potentials were examined for their abilities to degrade rat lung subendothelial matrix and purified basement membrane type IV collagen. Metastatic potentials were simultaneously determined based on the ability to form "...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-09-15 00:00:00
abstract：:Tumor production of parathyroid hormone-related protein (PTHRP) is responsible for most cases of hypercalcemia of malignancy. The transplantable rat Leydig tumor H-500 is known to cause hypercalcemia in rats by the release of abundant PTHRP and to closely reproduce the human syndrome. We have demonstrated recently tha...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-03-15 00:00:00
abstract：:Peripheral lymphocytes from cancer patients receiving mitomycin C treatment were examined for cytogenetic effects. The treatment consisted of i.v. injections of mitomycin C at a dose of 4 mg given twice a week for 2 weeks. The lymphocytes were cultured in vitro for 72 hr with phytohemagglutinin and 5-bromodeoxyuridine...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-02-01 00:00:00
abstract：:Four new human non-small cell lung cancer cell lines have been established in vitro. These cell lines have been characterized by (a) growth of a tumor in nude mice with histopathology similar to that of the primary, (b) isoenzyme patterns phenotypically human and distinct from each other, (c) distinguishing karyotypic...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:The estrogen receptor (ER) is a nuclear protein with a hormone- and a DNA-binding domain. We examined the DNA binding of ER in MCF-7 cells and 79 primary breast cancers by gel mobility shift assay using as a probe the estrogen response element (ERE). The mobility shift assay showed saturable, specific binding of ER to...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-07-01 00:00:00
abstract：:Monoclonal antibody (MAb) B72.3 was generated using a membrane-enriched fraction of a human mammary carcinoma biopsy. It has demonstrated reactivity to the majority of human adenocarcinomas including colorectal, gastric, pancreatic, ovarian, endometrial, mammary, and non-small cell lung cancer and no or weak reactivit...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-08-15 00:00:00
abstract：:Individual human infiltrating ductal carcinomas and fibroadenomas were sectioned frozen to yield an alternating sequence of stained and lyophilized material. Stained preparations were used as references permitting microdissection of regions of tumor involvement in the corresponding dried sections. Tissues quantities o...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-05-01 00:00:00
abstract：:A single cancer cell contains large numbers of genetic alterations that in combination create the malignant phenotype. However, whether amplified and mutated genes form functional and physical interaction networks that could explain the selection for cells with combined alterations is unknown. To investigate this issu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-3082
更新日期：2008-11-15 00:00:00
abstract：:Vascular thermotolerance in SCK tumors of A/J mice was studied by comparing the changes in blood flow, as measured by the 86Rb uptake method, from a single heating with those from two heatings. The heat-induced decline in 86Rb uptake in tumors could be substantially inhibited when the tumors were preheated, indicating...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:The distribution and localization of a glioma-associated antigen defined by monoclonal antibody 81C6 has been examined using human cultured cell lines and tissues. Monoclonal antibody 81C6 was selected from a hybridoma fusion of spleen cells of mice immunized with the glial fibrillary acidic protein-positive human gli...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-06-01 00:00:00
abstract：:Male inbred F344 weanling rats were fed semipurified diets containing 20 or 5% beef fats. At 7 weeks of age, all animals except controls were given 1,2-dimethylhydrazine [DMH (150 mg/kg body weight s.c.; one dose)], methylazoxymethanol acetate [MAM acetate (35 mg/kg body weight i.p.; one dose)], or methylnitrosourea (...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-11-01 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：:beta-Catenin is an ubiquitously expressed cytoplasmic protein that has a crucial role in both cadherin-mediated cell-cell adhesion and as a downstream signaling molecule in the wingless/Wnt pathway. Activating mutations in exon 3 of the beta-catenin gene, at the phosphorylation sites for ubiquitination and degradation...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-15 00:00:00
abstract：:Combinatorial strategies are needed to overcome the resistance of pancreatic cancer to immune checkpoint blockade (ICB). DNA damage activates the innate immune response and improves ICB efficacy. Because ATM is an apical kinase in the radiation-induced DNA damage response, we investigated the effects of ATM inhibition...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-19-0761
更新日期：2019-08-01 00:00:00
abstract：:Dietary factors can modify metabolic events involved in the initiation, promotion, or progression of tumors. To determine whether a high-sucrose diet has any effect on the development of enzyme-altered foci during the promotion step of chemical hepatocarcinogenesis in rats, 1-day-old Sprague-Dawley rats were given a s...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-06-01 00:00:00
abstract：:Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in pri...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-2654
更新日期：2010-01-01 00:00:00
abstract：:5-iododeoxyuridine (IdUrd) is highly effective in inducing the production of endogenous viruses (e.g., RNA-containing murine leukemia virus) from a variety of cell lines that normally do not release such viruses. For the activation of murine leukemia virus by IdUrd, its incorporation into cellular DNA is necessary. We...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-05-01 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：:The ShcA adaptor protein transduces oncogenic signals downstream of receptor tyrosine kinases. We show here that breast tumors engage the ShcA pathway to increase their metabolism. ShcA signaling enhanced glucose catabolism through glycolysis and oxidative phosphorylation, rendering breast cancer cells critically depe...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-3696
更新日期：2018-09-01 00:00:00
abstract：:A cell line derived from early passage of a transplantable tumor in athymic mice that initially had been injected with human breast adenocarcinoma cells produced a substantial amount of RNA sequences related to the Kirsten murine leukemia virus. The cell line derived from later passage of transplantation of these tumo...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
abstract：:The human melanoma cell line NEL-M1 proliferates in Ham's F-12 medium in the absence of serum, hormones, and growth factors. Culturing NEL-M1 cells in defined medium supplemented with insulin (5 micrograms/ml) and transferrin (5 micrograms/ml) results in a 94% increase in [3H]thymidine incorporation after 24 h and a 6...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:A model for medulloblastoma-like primitive neuroectodermal tumors was established in rat using retrovirally transduced SV40 large T antigen (LT) as an inducing agent (O. D. Wiestler et al., Brain Pathol., 2: 47-59, 1992). A cell line isolated from such a tumor and clonal derivatives thereof were biologically and molec...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1999-04-15 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
