Abstract:
:P-glycoprotein (Pgp), a member of the ATP-binding cassette family of transporters, is an important mediator of multidrug resistance in cancer. Pgp exhibits a very broad specificity for substrates. These substrates share a common feature of being amphipathic and can orient into either leaflet of the membrane bilayer. Current evidence suggests that Pgp recognizes and extracts substrates from the membrane bilayer, but from which leaflet is unresolved. To directly test whether Pgp can decrease substrate concentration in the extracellular leaflet of the plasma membrane in living cells, we used the fluorescent lipid analogue 1-[4-(trimethylamino)phenyl]-6-phenylhexa-1,3,5-triene (TMA-DPH). TMA-DPH in the extracellular solution rapidly partitions into the extracellular leaflet of the plasma membrane and exhibits slow transbilayer flipping into the cytoplasmic leaflet. Because TMA-DPH fluorescence is confined to the extracellular leaflet in early time points after addition but labels intracellular membranes after longer incubation, we can assess the effect of Pgp on TMA-DPH concentration from both extracellular leaflet and intracellular membranes. Transient transfection with a Pgp and the green fluorescence protein (GFP) fusion protein generated cells with heterogeneous expression levels of Pgp-GFP. Compared with nonexpressing cells, cells expressing Pgp-GFP showed decreased accumulation of TMA-DPH in intracellular membranes but similar levels of accumulation in the extracellular leaflet of the plasma membrane. Additionally, in drug-selected MCF7/Adr cells, which constitutively express high levels of Pgp, inhibition of Pgp by cyclosporin A resulted in significantly increased accumulation of TMA-DPH in intracellular membranes but no difference in its accumulation in the extracellular leaflet of the plasma membrane. These data indicate that whereas Pgp can extract TMA-DPH from the cytoplasmic leaflet of the membrane, any activity Pgp may possess in the extracellular leaflet is insufficient to decrease TMA-DPH concentration there and, therefore, does not contribute to lowering the cellular levels. Pgp is the prototype of an increasing number of clinically important ATP-binding cassette transporters of amphipathic drugs and lipids. These results may help decipher a common mechanism of these transporters.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Chen Y,Pant AC,Simon SMsubject
Has Abstractpub_date
2001-11-01 00:00:00pages
7763-9issue
21eissn
0008-5472issn
1538-7445journal_volume
61pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::The bcl-2 family of genes code for proteins that contain anti-apoptotic or pro-apoptotic activity. The human bfl-1 gene contains an open reading frame for a 175-amino acid Bcl-2 family protein. Among the various Bcl-2 family members, the Bfl-1 protein shares the highest homology with the mouse A1 protein. These two pr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::We have studied the sensitivities of four hematopoietic stem cell types to heat stress as well as their abilities to develop thermotolerance. Granulocyte-macrophage colony forming units were the most heat resistant bone marrow progenitors tested. Of the erythroid progenitors tested, erythrocyte colony forming units we...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::We have reported previously that the PTEN COOH-terminal 33 amino acids play a role in the maintenance of PTEN protein stability (Tolkacheva and Chan, Oncogene, 19: 680-689, 2000). By site-directed mutagenesis, we identified two threonine residues within this COOH-terminal region at codon 382 and 383 that may be target...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::12-O-Tetradecanoylphorbol-13-acetate (TPA) is widely used as a tumor promoter with organotropy in skin and esophagus. TPA-induced, organ-specific tumor promotion is not correlated with the distribution of its receptor, protein kinase C (PKC). Using five administration methods (painting, drinking, gavage feeding, i.p. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-15 00:00:00
abstract::One major rationale for using interleukin-2 and IFN-alpha in cancer immunotherapy is to activate tumor-specific T cells at the tumor site. To study the in situ T-cell response, we determined the T-cell receptor (TCR) repertoire in six melanoma metastases regressing after cytokine treatment obtained from five patients....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-07-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer deaths in the United States. The deoxynucleoside analogue gemcitabine is among the most effective therapies to treat PDAC, however, nearly all patients treated with gemcitabine either fail to respond or rapidly develop resistance. One hallmark of PDA...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0960
更新日期:2019-11-15 00:00:00
abstract::RNA-DNA saturation hybridization experiments were used to estimate the extent of transcription of repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. Measurements were made with RNA from nontransformed cells in both the subconfluent and confluent stages of growth, transformed cel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-06-01 00:00:00
abstract::We have recently identified human epidermal growth factor-like immunoreactive factor synthesized and secreted by human breast cancer cells (MCF-7) as a secretory protein encoded by the pS2 gene, the transcription of which is directly induced by estrogen. We demonstrated in this paper that synthesis and secretion of pS...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 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::Proliferating mammalian stem and cancer cells express telomerase [telomerase reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and maintain telomere ends. Telomerase-expressing cells also have higher levels of the single-stranded DNA-binding protein SSB1, which has a critical role in DNA dou...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-2289
更新日期:2015-03-01 00:00:00
abstract::The intention of this study was to estimate the pharmacological advantage of a clinically applicable method of isolated liver perfusion (ILP) over hepatic artery infusion (HAI) administering various doses of 5-fluorouracil (FUra). FUra concentrations were measured using high-performance liquid chromatography in liver ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-03-15 00:00:00
abstract::Given that there are millions of single-nucleotide polymorphisms (SNPs) in the entire human genome, a major difficulty faced by scientists in planning costly population-based genotyping is to choose target SNPs that are most likely to affect phenotypic functions and ultimately contribute to disease development. Althou...
journal_title:Cancer research
pub_type: 杂志文章,meta分析
doi:10.1158/0008-5472.can-03-2800
更新日期:2004-03-15 00:00:00
abstract::Activities of the adenine purine nucleotide cycle enzymes, i.e., adenylosuccinate (SAMP) synthetase, SAMP lyase, and adenosine 5'-monophosphate deaminse, were determined in hepatic tissue of rats fed and/or given injections of 3'-methyl-4-dimethylaminoazobenzene, 4'-methyl-4-dimethylaminoazobenzene, thioacetamide, eth...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::EphB4 receptor and its ligand ephrinB2 play an important role in vascular development during embryogenesis. In blood vessels, ephrinB2 is expressed in arterial endothelial cells (EC) and mesenchymal supporting cells, whereas EphB4 is only expressed in venous ECs. Previously, we reported that OP9 stromal cells, which s...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0531
更新日期:2007-10-15 00:00:00
abstract::Intrahepatic cholangiocarcinoma (IHCC) is a primary cancer of the liver with an increasing incidence and poor prognosis. Preclinical studies of the etiology and treatment of this disease are hampered by the relatively small number of available IHCC cell lines or genetically faithful animal models. Here we report the d...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3596
更新日期:2012-03-15 00:00:00
abstract::Fusions of the ETV6/TEL gene to receptor or protein tyrosine kinases (TKs), such as PDGFRbeta, JAK2, ABL, ABL2, TRKC, and Syk, have been reported in various hematological malignancies. Expression of the resultant chimeric proteins is believed to lead to constitutive TK activity through activation by the helix-loop-hel...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-12-01 00:00:00
abstract::To determine whether infection with a Helicobacter pylori strain possessing cagA is associated with an increased risk of development of adenocarcinoma of the stomach, we used a nested case-control study based on a cohort of 5443 Japanese-American men in Oahu, Hawaii, who had a physical examination and a phlebotomy dur...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-05-15 00:00:00
abstract::Tumor recurrence in prostate cancer has been attributed to the presence of CD44-expressing tumor-initiating cells. In this study, we report that miR-708 is a key negative regulator of this CD44(+) subpopulation of prostate cancer cells, with important implications for diagnosis and prognosis of this disease. miR-708 w...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-0540
更新日期:2012-07-15 00:00:00
abstract::Overexpression of ABCB1 (MDR1) P-glycoprotein, a multidrug efflux pump, is one mechanism by which tumor cells may develop multidrug resistance (MDR), preventing the successful chemotherapeutic treatment of cancer. Sesquiterpenes from Celastraceae family are natural compounds shown previously to reverse MDR in several ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1005
更新日期:2004-10-01 00:00:00
abstract::Driver tyrosine kinase mutations are rare in sarcomas, and patterns of tyrosine phosphorylation are poorly understood. To better understand the signaling pathways active in sarcoma, we examined global tyrosine phosphorylation in sarcoma cell lines and human tumor samples. Anti-phosphotyrosine antibodies were used to p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3015
更新日期:2012-05-15 00:00:00
abstract::The combinations of amphotericin B (AmB) with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-cyclohexyl isocyanate, the carbamoylating decomposition product of CCNU, were more potent in lysing HL-60 cells than the combinations of AmB with 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) or 2-chloroethyl isocyana...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Current standard of care for patients with pediatric acute lymphoblastic leukemia (ALL) is mainly effective, with high remission rates after treatment. However, the genetic perturbations that give rise to this disease remain largely undefined, limiting the ability to address resistant tumors or develop less toxic targ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1303
更新日期:2017-01-15 00:00:00
abstract::We used antibody microarrays to probe the associations of multiple serum proteins with pancreatic cancer and to explore the use of combined measurements for sample classification. Serum samples from pancreatic cancer patients (n = 61), patients with benign pancreatic disease (n = 31), and healthy control subjects (n =...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1436
更新日期:2005-12-01 00:00:00
abstract::Previous studies have suggested a "catalytic role" in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPC). However, preclinical and clinical studies have shown that the quantitative role of marrow-derived EPCs in cancer vascularization is extremely variable. We hav...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-1739
更新日期:2012-01-01 00:00:00
abstract::Bloom syndrome is an autosomal recessive disorder whose characteristics include an increased risk for many types of cancers. In contrast to the homozygous mutations of Bloom syndrome, heterozygous carriers of BLM mutations may be at increased risk for developing colorectal cancer. We have screened 2,333 Jewish individ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-04-15 00:00:00
abstract::Eight analogues of 2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone have been synthesized and tested for cytotoxicity against four different leukemic and lymphomic cell lines. For K562 and BSM cells, the toxicity could be correlated with the ease of reduction of the compounds as determined by the one-electr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-04-01 00:00:00
abstract::Hematogenous carcinoma metastasis is supported by aggregated platelets and leukocytes, forming tumor cell emboli. Early tumor cell-platelet interactions can be mediated by P-selectin binding to tumor cell surface ligands and this process is blocked by heparin. We previously showed that L-selectin deficiency also atten...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3121
更新日期:2006-02-01 00:00:00
abstract::Although aberrant microRNA (miRNA) is expressed in different types of human cancer tissues, its pathophysiologic role and the relevance of tumorigenesis and metastasis are still largely unknown. Here, we defined miRNAs involved in cancer metastasis (metastamirs) using an established mouse model for peritoneal dissemin...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-2530
更新日期:2011-02-15 00:00:00
abstract::DAB486IL-2, a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with interleukin-2 (IL-2), has displayed significant activity in patients with chemotherapy refractory hematological cancers. To further investigate the safety and antitumor effect of this agent, we...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::We have previously reported that rodent tumor cell lines secrete a potent vascular permeability factor with a molecular weight of 34,000-42,000 (Senger et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science (Wash. DC), 219: 983-985, 1983). This tumor-secreted vas...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00