Arginine 482 to glycine mutation in ABCG2/BCRP increases etoposide transport and resistance to the drug in HEK-293 cells.

Abstract:

:Resistance to etoposide has been associated with the overexpression of P-glycoprotein and MRP1 in human tumor cells. However, the role of BCRP in resistance to etoposide has not been clearly established, especially the significance of arginine 482 mutations in drug transport (cellular uptake and efflux). Different levels of resistance to etoposide have been recently observed in cells expressing BCRP in terms of cytotoxicity. The aim of this work was to study the effects of these mutations on the functional involvement of BCRP in etoposide transport. HEK293 cells were transfected with an empty vector (HEK/V), the vector bearing the wild-type BCRP (HEK/R482), the mutant arginine-482-glycine (HEK/R482G) or the mutant arginine-482-threonine (HEK/R482T). MTT assay was used to study the cytotoxic effect of etoposide and [3H]-etoposide was used to determine cellular drug uptake and efflux. Data show that HEK/R482G cells displayed the highest levels of resistance to etoposide. Cellular [3H]-etoposide uptake was lower in HEK/R482, HEK/R482G and HEK/R482T cells compared to HEK/V cells. In addition, cellular [3H]-etoposide uptake in HEK/R482G was the lowest. Drug efflux measurements showed that fumitremorgin C was able to increase the residual cellular [3H]-etoposide uptake in BCRP-transfected cells and especially in HEK/R482G ones. Our data show that the R482G mutation in BCRP is able to increase efflux of etoposide and that mutation analysis at codon 482 may be of clinical importance in cancers treated with etoposide.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Eddabra L,Wenner T,El Btaouri H,Baranek T,Madoulet C,Cornillet-Lefebvre P,Morjani H

doi

10.3892/or.2011.1468

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

232-7

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

27

pub_type

杂志文章
  • TGF‑β1‑induced epithelial‑mesenchymal transition increases fatty acid oxidation and OXPHOS activity via the p‑AMPK pathway in breast cancer cells.

    abstract::Breast cancer is the most common malignancy in women, and metastasis is the leading cause of death in breast cancer patients. Previous studies have shown that epithelial‑mesenchymal transition (EMT) is involved in the metastasis of breast cancer, but the metabolic reprogramming and regulation mechanisms involved in th...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7661

    authors: Liu QQ,Huo HY,Ao S,Liu T,Yang L,Fei ZY,Zhang ZQ,Ding L,Cui QH,Lin J,Yu M,Xiong W

    更新日期:2020-09-01 00:00:00

  • Tannic acid attenuates hepatic oxidative stress, apoptosis and inflammation by activating the Keap1‑Nrf2/ARE signaling pathway in arsenic trioxide‑toxicated rats.

    abstract::The present study was performed to investigate the protective effects of tannic acid (TA) on liver injury induced by arsenic trioxide (ATO) and to elucidate the mechanism involved as related to the Kelch‑like ECH‑associated protein 1 (Keap1)‑nuclear factor erythroid 2‑related factor 2 (Nrf2)/antioxidant response eleme...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2020.7764

    authors: Li M,Liu P,Xue Y,Liang Y,Shi J,Han X,Zhang J,Chu X,Chu L

    更新日期:2020-11-01 00:00:00

  • Decreased miRNA-148a is associated with lymph node metastasis and poor clinical outcomes and functions as a suppressor of tumor metastasis in non-small cell lung cancer.

    abstract::Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, and only 15% of lung cancer patients live more than 5 years. microRNAs (miRNAs) are endogenously expressed non-coding RNAs, and dysregulation of miRNAs is a common feature in human cancers including lung cancer. In this study, w...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2611

    authors: Chen Y,Min L,Zhang X,Hu S,Wang B,Liu W,Wang R,Gu X,Shen W,Lv H,Zou J,Chen Y,Xu X,Chen L

    更新日期:2013-10-01 00:00:00

  • miR-216b inhibits glioma cell migration and invasion through suppression of FoxM1.

    abstract::MicroRNAs (miRNAs) play a vital role in tumour biological and pathologic processes. In the present study, we aimed to detect the expression and biological role of miR-216b in glioma. Our data showed that miR-216b was significantly downregulated in human glioma tissues and cells. Ectopic expression of miR-216b inhibite...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5824

    authors: Zhang T,Ma G,Zhang Y,Huo H,Zhao Y

    更新日期:2017-09-01 00:00:00

  • CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood‑brain barrier permeability in tumor brain metastasis.

    abstract::The blood‑brain barrier (BBB) constitutes an efficient organization of tight junctions that limits the delivery of tumor to the brain. The principal tight junction protein in BBB is claudin‑5 (CLDN5), but its mechanism of action remains largely unknown. Long non‑coding RNAs (lncRNAs) are aberrantly expressed in many c...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6208

    authors: Ma SC,Li Q,Peng JY,Zhouwen JL,Zhang DN,Zhang CB,Jiang WG,Jia W

    更新日期:2018-03-01 00:00:00

  • Zoledronic acid increases the antitumor effect of gefitinib treatment for non-small cell lung cancer with EGFR mutations.

    abstract::Non-small cell lung cancer (NSCLC) patients with epithelial growth factor receptor (EGFR) mutations and bone metastases are often concurrently administered tyrosine kinase inhibitors (TKIs) and bisphosphonates. Yet, the effects and mechanisms of these agents are unclear. In the present study, we aimed to ascertain whe...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4741

    authors: Feng C,Liu X,Li X,Guo F,Huang C,Qin Q,Wang Y

    更新日期:2016-06-01 00:00:00

  • Changes in bone resorption and vascular endothelial growth factor after a single zoledronic acid infusion in cancer patients with bone metastases from solid tumours.

    abstract::Zoledronic acid (Zometa, ZOL) is increasingly used to treat tumour-induced bone disease, and is also reported to have antiangiogenic properties in vivo. In this study, we have investigated the correlations between changes in the proangiogenic cytokine, vascular endothelial growth factor (VEGF), and markers of bone res...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Santini D,Vincenzi B,Hannon RA,Brown JE,Dicuonzo G,Angeletti S,La Cesa A,Coleman RE,Tonini G,Budillon A,Caraglia M,Holen I

    更新日期:2006-05-01 00:00:00

  • Absence of Bcl10 gene mutations in Ewing's sarcomas.

    abstract::The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas. Somatic mutations of Bcl10 were found in not only t(1;14)-bearing MALT lymphomas, but also a wide range of other tumors. To clarify the actual frequency and spectrum of Bcl10 mutat...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.6.1333

    authors: Park YK,Chi SG,Unni KK

    更新日期:2001-11-01 00:00:00

  • Rab15 alternative splicing is altered in spheres of neuroblastoma cells.

    abstract::Neuroblastoma is an aggressive pediatric tumor that accounts for 15% of cancer-related deaths in children. More than half of high-risk neuroblastoma patients develop tumor relapse that is lethal in most cases. A small population of tumor-initiating cells (TICs), recently identified from high-risk neuroblastoma patient...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1731

    authors: Pham TV,Hartomo TB,Lee MJ,Hasegawa D,Ishida T,Kawasaki K,Kosaka Y,Yamamoto T,Morikawa S,Yamamoto N,Kubokawa I,Mori T,Yanai T,Hayakawa A,Takeshima Y,Iijima K,Matsuo M,Nishio H,Nishimura N

    更新日期:2012-06-01 00:00:00

  • Chemokines mediate mesenchymal stem cell migration toward gliomas in vitro.

    abstract::Previous studies have demonstrated the tremendous tropism of mesenchymal stem cells (MSCs) for malignant gliomas, making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells. However, the mechanisms underlying the tropism of MSCs for gliomas remain poorly defined. It has been ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or_00000796

    authors: Xu F,Shi J,Yu B,Ni W,Wu X,Gu Z

    更新日期:2010-06-01 00:00:00

  • Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells.

    abstract::Gastric cancer (GC) is one of the most common malignancies, and is the second leading cause of cancer-related deaths worldwide. Macrophages infiltrated in the tumor microenvironment (TME) called tumor-associated macrophages (TAMs) are key orchestrators in TME. In GC, it has been reported that infiltration of TAMs is a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.5877

    authors: Guo J,Yan Y,Yan Y,Guo Q,Zhang M,Zhang J,Goltzman D

    更新日期:2017-10-01 00:00:00

  • Transcriptional silencing of ETS-1 abrogates epithelial-mesenchymal transition resulting in reduced motility of pancreatic cancer cells.

    abstract::v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays crucial roles in a spectrum of malignancies. ETS-1 has gained attention in cancer research for its importance in cell migration, invasion and proliferation. In the present study, we focused on the effect of ETS-1 on epithelial-mesenchymal transition (EM...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2014.3613

    authors: Li C,Wang Z,Chen Y,Zhou M,Zhang H,Chen R,Shi F,Wang C,Rui Z

    更新日期:2015-02-01 00:00:00

  • Suppression of Elk1 inhibits thyroid cancer progression by mediating PTEN expression.

    abstract::ETS‑domain containing protein (Elk1) is reported to be a member of the ETS oncogene family, and promotes tumorigenesis in cancer such as bladder, prostate and ovarian. Nevertheless, the role of Elk1 in thyroid cancer progression remains unclear. In the present study, we aimed to investigate the role and underlying mol...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2018.6554

    authors: Kong Y,Yin J,Fu Y,Chen Y,Zhou Y,Geng X

    更新日期:2018-09-01 00:00:00

  • Differential effects of raloxifene and tamoxifen on the expression of estrogen receptors and antigen Ki-67 in human endometrial adenocarcinoma cell line.

    abstract::Tamoxifen and raloxifene are widely used in clinical practice. It has been found that tamoxifen treatment increases the risk of development of endometrial cancer. The effects of tamoxifen and raloxifene on endometrium might be caused by different estrogen receptor expression. The aim of the present study was immunohis...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Koda M,Jarzabek K,Haczynski J,Knapp P,Sulkowski S,Wolczynski S

    更新日期:2004-09-01 00:00:00

  • Multiparameter analysis using cell cycle biomarkers for small-size lung adenocarcinoma: prognostic implications.

    abstract::Cell cycle-related molecules play crucial roles in maintaining genomic stability, and can also serve as biomarkers of cell cycle phase distribution at the same time. In this study, we used multiparameter analysis of various biomarkers to investigate their utility for the evaluation ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1894

    authors: Haruki T,Shomori K,Shiomi T,Taniguchi Y,Nakamura H,Ito H

    更新日期:2012-09-01 00:00:00

  • miR-141 confers docetaxel chemoresistance of breast cancer cells via regulation of EIF4E expression.

    abstract::Resistance to docetaxel, a chemotherapy drug for breast cancer (BC) treatment, occurs in ~50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through miR-141 has been proven to play an important role in cancer drug resistance. The present study investig...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2015.3866

    authors: Yao YS,Qiu WS,Yao RY,Zhang Q,Zhuang LK,Zhou F,Sun LB,Yue L

    更新日期:2015-05-01 00:00:00

  • An antibody assay predictive of BRCA1 mutations in ovarian tumors and normal tissue.

    abstract::To determine whether immunohistochemistry can identify BRCA1 mutations, immunohistochemical (IH) analysis was undertaken on paraffin sections of paired ovarian cancer and normal tissue using antibodies against both terminal regions of the BRCA1 protein. Ten patients at risk for BRCA1 mutations were studied. The result...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.7.5.949

    authors: Byrne TJ,Reece MT,Adams LA,Lane MA,Cohn GM

    更新日期:2000-09-01 00:00:00

  • Quercetin acts as an antioxidant and downregulates CYP1A1 and CYP1B1 against DMBA-induced oxidative stress in mice.

    abstract::We investigated the effects of quercetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced oxidative stress and the expression of CYP1A1 and CYP1B1 in mice. Quercetin was administered orally to mice at 100 or 250 mg/kg BW for 18 days, after which DMBA (34 mg/kg BW) was administered intragastrically twice. Quercetin sho...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1753

    authors: Choi EJ,Kim T,Kim GH

    更新日期:2012-07-01 00:00:00

  • Rapamycin induces p53-independent apoptosis through the mitochondrial pathway in non-small cell lung cancer cells.

    abstract::The mammalian target of rapamycin (mTOR) is a key kinase acting downstream of growth factor receptor PI3K and AKT signaling, leading to processes resulting in increased cell size and proliferation through translation control. Rapamycin, a specific inhibitor of mTOR, results predomin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1855

    authors: Miyake N,Chikumi H,Takata M,Nakamoto M,Igishi T,Shimizu E

    更新日期:2012-09-01 00:00:00

  • Metronomic treatment of temozolomide inhibits tumor cell growth through reduction of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas.

    abstract::Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide (TMZ), a methylating agent is one of the most effective chemotherapeutic agents against glioblastoma. To overcome the problem that most of these tumors become resistant to chemotherapeutic regimens within a year, we investigated the antitu...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Kim JT,Kim JS,Ko KW,Kong DS,Kang CM,Kim MH,Son MJ,Song HS,Shin HJ,Lee DS,Eoh W,Nam DH

    更新日期:2006-07-01 00:00:00

  • The inhibition of growth and angiogenesis in heterotransplanted esophageal carcinoma via intratumoral injection of arsenic trioxide.

    abstract::To investigate the antitumor action of arsenic trioxide (As2O3) by intratumoral injection into solid tumors, tumor growth inhibition (TGI) and angiogenesis of heterotransplanted esophageal carcinoma in mice was carried out. The cultured human esophageal carcinoma cells were inoculated into both laterals of the abdomin...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:

    authors: Shen ZY,Shen J,Chen MH,Wu XY,Wu MH,Zeng Y

    更新日期:2003-11-01 00:00:00

  • The newly synthesized 2-(3-hydroxy-5-methoxyphenyl)-6,7-methylenedioxyquinolin-4-one triggers cell apoptosis through induction of oxidative stress and upregulation of the p38 MAPK signaling pathway in HL-60 human leukemia cells.

    abstract::The aim of the present study was to discover the signaling pathways associated with 2-(3-hydroxy-5-methoxy-phenyl)-6,7-methylenedioxyquinolin-4-one (YYK1)-induced apoptosis in HL-60 human leukemia cells. YYK1 induced cytotoxic effects, cell morphological changes, decreased the cell ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.1923

    authors: Cheng YY,Yang JS,Tsai SC,Liaw CC,Chung JG,Huang LJ,Lee KH,Lu CC,Chien HC,Tsuzuki M,Kuo SC

    更新日期:2012-10-01 00:00:00

  • Inhibition of autophagy enhances the targeted therapeutic effect of sorafenib in thyroid cancer.

    abstract::The multi-target kinase inhibitor sorafenib has been approved for the treatment of patients with advanced differentiated thyroid cancer. However, different sensitivities to sorafenib have been observed, and few patients have benefited from sorafenib treatment in the long term. In the event of acquired resistance to so...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2017.6118

    authors: Yi H,Ye T,Ge M,Yang M,Zhang L,Jin S,Ye X,Long B,Li L

    更新日期:2018-02-01 00:00:00

  • Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro.

    abstract::We investigated cell susceptibility to hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines (RYSTs) and attempted to correlate this with the known potentially relevant molecular determinants of apoptosis, p53 protein status, Bcl-2 family of proteins and heat shock proteins (Hsp). Parent cell line, NMT-1...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.8.3.501

    authors: Islam MS,Mitsuhashi N,Akimoto T,Sakurai H,Hasegawa M,Ishikawa H,Niibe H

    更新日期:2001-05-01 00:00:00

  • Genome-wide profiling of long non-coding RNA expression patterns in the EGFR-TKI resistance of lung adenocarcinoma by microarray.

    abstract::Mutations in the epidermal growth factor receptor (EGFR) make lung adenocarcinoma cells sensitive to EGFR tyrosine kinase inhibitors (TKIs). Long-term cancer therapy may cause the occurrence of acquired resistance to EGFR TKIs. Long non-coding RNAs (lncRNAs) play important roles in tumor formation, tumor metastasis an...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2016.4758

    authors: Wu Y,Yu DD,Hu Y,Yan D,Chen X,Cao HX,Yu SR,Wang Z,Feng JF

    更新日期:2016-06-01 00:00:00

  • Angiogenesis and the immune response as targets for the prevention and treatment of colorectal cancer (review).

    abstract::The carcinogenic process in previously normal human colonic mucosa involves hyperproliferation and adenoma formation, but it is not known why only a tiny proportion of adenomas undergo malignant transformation. There is accumulating evidence in favour of the hypothesis that inflammatory processes are a prerequisite fo...

    journal_title:Oncology reports

    pub_type: 杂志文章,评审

    doi:

    authors: Sharma RA,Dalgleish AG,Steward WP,O'Byrne KJ

    更新日期:2003-09-01 00:00:00

  • Possible mechanism of growth inhibition by Scutellaria baicalensis in an estrogen-responsive mouse tumor cell line.

    abstract::We have studied the effects of Saiboku-to, a traditional Chinese medicine having suppressive activities for leukotriene production and release, on the proliferation of the estrogen-responsive mouse Leydig tumor cell line B-1F. In our previous reports, it is shown that Saiboku-to promotes, but Scutellaria baicalensis, ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1196

    authors: Murashima T,Katayama H,Shojiro K,Nishizawa Y

    更新日期:2011-05-01 00:00:00

  • Mechanism of the inhibition of the STAT3 signaling pathway by EGCG.

    abstract::Signal transducer and activator of transcription 3 (STAT3) is an oncogene that promotes cell survival, proliferation, and motility. In the present study, we explored the mechanism involved in the inhibition by epigallocatechin-3-gallate (EGCG) of STAT3 signaling as detected by surface plasmon resonance (SPR)-binding a...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2013.2743

    authors: Wang Y,Ren X,Deng C,Yang L,Yan E,Guo T,Li Y,Xu MX

    更新日期:2013-12-01 00:00:00

  • Vimentin expression is associated with decreased survival in gastric cancer.

    abstract::Gastric cancer rich in stromal tissue, such as diffuse-type disease, carries a poor prognosis. In some cancers, expression of vimentin, a mesenchymal maker, is associated with poor survival. The expression of mesenchymal markers such as vimentin is observed after epithelial-mesenchymal transition (EMT), an important i...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2011.1185

    authors: Otsuki S,Inokuchi M,Enjoji M,Ishikawa T,Takagi Y,Kato K,Yamada H,Kojima K,Sugihara K

    更新日期:2011-05-01 00:00:00

  • Few genes are associated with the capability of pancreatic ductal adenocarcinoma cells to grow in the liver of nude rats.

    abstract::Owing to aggressiveness and chemoresistance, pancreatic ductal adenocarcinoma (PDAC) is characterised by a poor prognosis. To address this disease-spe-cific dilemma we aimed to establish animal models, which can be used for identifying new specific tumor markers, as well as serving ...

    journal_title:Oncology reports

    pub_type: 杂志文章

    doi:10.3892/or.2012.2049

    authors: Eyol E,Murtaga A,Zhivkova-Galunska M,Georges R,Zepp M,Djandji D,Kleeff J,Berger MR,Adwan H

    更新日期:2012-12-01 00:00:00