Long‑term exposure to gefitinib induces acquired resistance through DNA methylation changes in the EGFR‑mutant PC9 lung cancer cell line.

Abstract:

:This study was designed to identify epigenetically regulated genes and to clarify the contribution of epige-netic alteration to acquired resistance to epidermal growth factor receptor‑tyrosine kinase inhibitors (EGFR‑TKIs). We established a gefitinib‑resistant lung cancer cell line, PC9, which was originally gefitinib‑sensitive, by serial long‑term exposure to gefitinib. RNA and DNA were collected from both gefitinib‑sensitive and ‑resistant PC9 cells, and comprehensive DNA methylation and mRNA expression analyses were performed using Infinium HumanMethylation27 Bead Arrays and Agilent SurePrint G3 Human Gene Expression 8x60K Array, respectively. DNA methylation was increased in 640 genes in gefitinib‑resistant cells compared to parental cells. Among them, we selected 29 candidate genes that presented a decrease in mRNA expression in resistant PC9. We further studied four of the selected genes (C10orf116, IGFBP3, KL, and S100P) and found that KL or S100P silencing by siRNA induced a decrease in gefitinib sensitivity compared to that in the negative control in PC9. In conclusion, KL and S100P could be potential targets to overcome resistance to EGFR‑TKIs.

journal_name

Int J Oncol

authors

Terai H,Soejima K,Yasuda H,Sato T,Naoki K,Ikemura S,Arai D,Ohgino K,Ishioka K,Hamamoto J,Kanai Y,Betsuyaku T

doi

10.3892/ijo.2014.2733

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

430-6

issue

1

eissn

1019-6439

issn

1791-2423

journal_volume

46

pub_type

杂志文章
  • Resistance to cisplatin-induced apoptosis via PI3K-dependent survivin expression in a rat hepatoma cell line.

    abstract::Hepatocellular carcinoma (HCC) is known to be resistant to chemotherapy. Survivin, a member of the inhibitor of apoptosis proteins, is overexpressed in most cancers but is absent in most normal adult tissue. The aim of this study was to investigate whether expression of survivin contributes to resistance to cisplatin-...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Asechi H,Hatano E,Nitta T,Tada M,Iwaisako K,Tamaki N,Nagata H,Narita M,Yanagida A,Ikai I,Uemoto S

    更新日期:2010-07-01 00:00:00

  • Multiple regions with allelic loss at chromosome 3 in superficial multifocal bladder tumors.

    abstract::We have examined six patients with multiple low grade, low stage superficial multifocal bladder tumors with surrounding tissues for loss of heterozygosity (LOH) and microsatellite instability at chromosome 3, totaling 76 samples. The majority (4/5) of the patients had LOH at or close to the fragile histidine triad (FH...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.18.1.203

    authors: Louhelainen J,Wijkström H,Hemminki K

    更新日期:2001-01-01 00:00:00

  • Hepatic arterial bolus chemotherapy for colorectal metastases using an implantable port.

    abstract::Twenty-one patients with isolated colorectal liver metastases underwent hepatic artery infusion (HAI) port implantation for regional chemotherapy with bolus injections of 5-FU, LV and fast drip of cisplatin. Ten of the 21 patients had previously failed systemic chemotherapy before HAI. Toxicity was moderate and no nee...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.6.1295

    authors: Lyass S,Lyass O,Gabizon A,Peretz T,Eid A,Muggiasullam M,Durst A,Shiloni E

    更新日期:1996-12-01 00:00:00

  • Inhibition of MMP-9 using a pyrrole-imidazole polyamide reduces cell invasion in renal cell carcinoma.

    abstract::We investigated the clinical significance of the expression levels of matrix metalloproteinase 9 (MMP-9) in renal cell carcinoma (RCC). In addition, we validated the efficacy of pyrrole imidazole polyamide (PIP) targeting MMP-9 on inhibiting proliferation and invasion of RCC. We evaluated the expression levels of MMP-...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.2073

    authors: Sato A,Nagase H,Obinata D,Fujiwara K,Fukuda N,Soma M,Yamaguchi K,Kawata N,Takahashi S

    更新日期:2013-11-01 00:00:00

  • GBP1 promotes erlotinib resistance via PGK1‑activated EMT signaling in non‑small cell lung cancer.

    abstract::Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‑TKI), is widely applied as a first‑line treatment for non‑small cell lung cancer (NSCLC) and greatly improves the clinical outcomes of patients. However, acquired resistance to EGFR‑TKIs remains a major clinical challenge. Here, we identifi...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5086

    authors: Cheng L,Gou L,Wei T,Zhang J

    更新日期:2020-09-01 00:00:00

  • Cancer-reactive memory T cells from bone marrow: Spontaneous induction and therapeutic potential (Review).

    abstract::Cognate interactions between naïve tumor antigen (TA)-specific T cells and TA-presenting dendritic cells (DCs) are facilitated by secondary lymphoid organs such as lymph nodes or the spleen. These can result either in TA-specific tolerance or, depending on environmental costimulatory signals, in TA-specific immune res...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2015.3197

    authors: Schirrmacher V

    更新日期:2015-12-01 00:00:00

  • 5-ht3 antagonist ondansetron for the treatment of chemotherapy-induced nausea and vomiting in an outpatient population.

    abstract::Prevention of chemotherapy induced nausea and vomiting in an outpatient population requires an antiemetic regimen which is reliable and safe and easy to administer. In this study the use of oral ondansetron was investigated in 45 patients receiving 143 courses of non-cisplatin containing chemotherapy regimens on an ou...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.4.6.1283

    authors: Casper J,Casper S,Kohnewompner C,Bokemeyer C,Hecker H,Schmoll H

    更新日期:1994-06-01 00:00:00

  • Silencing LPAATβ inhibits tumor growth of cisplatin-resistant human osteosarcoma in vivo and in vitro.

    abstract::Cisplatin-resistance has become a major impediment in the medical treatment of cancers such as osteosarcoma, the most common primary malignancy of bone. Since lysophosphatidic acid acyltransferase β (LPAATβ) was reported to be critically involved in osteosarcoma, our study investigated the role of LPAATβ in human oste...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3820

    authors: Song L,Duan P,Gan Y,Li P,Zhao C,Xu J,Zhang Z,Zhou Q

    更新日期:2017-02-01 00:00:00

  • HIF1-positive and HIF1-negative glioblastoma cells compete in vitro but cooperate in tumor growth in vivo.

    abstract::Glioblastoma multiforme (GBM) is characterized by extensive angiogenesis that is mostly orchestrated by the hypoxia inducible factor HIF-1. Deregulation of HIF-1 is believed to contribute to cancer initiation and progression. However, instances have been described in which loss of HIF-1 leads to more aggressive tumors...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000554

    authors: Fiorenzo P,Mongiardi MP,Dimitri D,Cozzolino M,Ferri A,Montano N,Trevisi G,Maira G,Battistini L,Falchetti ML,Levi A,Pallini R

    更新日期:2010-04-01 00:00:00

  • p53 and cyclin D1 protein expression in glottic laryngeal squamous cell carcinomas involving the anterior commissure (pT1bN0M0).

    abstract::The prognosis of patients carrying glottic squamous cell carcinomas (GSCCs) involving the anterior commissure is often unpredictable. In order to assess the possible prognostic role of new and reliable parameters, p53 and cyclin D1 protein expression was immunohistochemically analysed in pathological samples from 27 p...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.9.3.553

    authors: Pignataro L,Capaccio P,Pruneri G,Carboni N,Fracchiolla N,Richelda R,Scaramellini G,Neri A,Buffa R

    更新日期:1996-09-01 00:00:00

  • Genome-wide profiling of long non-coding RNA expression patterns in anthracycline-resistant breast cancer cells.

    abstract::Long non-coding RNAs (lncRNAs) are involved in cancer progression. In the present study, we analyzed the lncRNA profiles in adriamycin-resistant and -sensitive breast cancer cells and found a group of dysregulated lncRNAs in the adriamycin-resistant cells. Expression of the dysregulated lncRNAs was correlated with dys...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2016.3665

    authors: He DX,Zhang GY,Gu XT,Mao AQ,Lu CX,Jin J,Liu DQ,Ma X

    更新日期:2016-10-01 00:00:00

  • P-glycoprotein-mediated multidrug resistance is modulated by pretreatment with chemosensitizers in HCT-8 carcinoma cells in vitro.

    abstract::The effects of pretreatment with the multidrug resistance (MDR) modulators verapamil (VPM), tamoxifen (TMX), cyclosporin A (CsA), and SDZ PSC833 (PSC) on drug sensitivity of the P-glycoprotein (Pgp) expressing human ileocecal carcinoma cell line HCT-8 is described. Following pretreatment of 2, 16 and 48 h with the ind...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.12.5.1137

    authors: Haberl I,Swatonek H,Schaufler K,Ulsperger E,Wenzl E,Theyer G,Hamilton G,Thalhammer T

    更新日期:1998-05-01 00:00:00

  • Reduced Fhit protein expression and loss of heterozygosity at FHIT gene in tumours from smoking and asbestos-exposed lung cancer patients.

    abstract::The FHIT gene, at 3p14.2, has been suggested to form a molecular target to damage induced by human lung carcinogens. We examined aberrant expression of the Fhit protein and allele loss at the FHIT gene in a series of lung cancer cases, mainly of non-small cell carcinoma (NSCLC) histology. We had detailed data on tobac...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Pylkkanen L,Wolff H,Stjernvall T,Tuominen P,Sioris T,Karjalainen A,Anttila S,Husgafvel-Pursiainen K

    更新日期:2002-02-01 00:00:00

  • Several fusion genes identified by whole transcriptome sequencing in a spindle cell sarcoma with rearrangements of chromosome arm 12q and MDM2 amplification.

    abstract::Spindle cell tumors are clinically heterogeneous but morphologically similar neoplasms that can occur anywhere, mostly in adult patients. They are treated primarily with surgery to which is often added adjuvant or neoadjuvant radiation. Sub-classification of spindle cell sarcomas requires integration of histology, cli...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2605

    authors: Panagopoulos I,Bjerkehagen B,Gorunova L,Berner JM,Boye K,Heim S

    更新日期:2014-11-01 00:00:00

  • Long non‑coding RNAs in HBV‑related hepatocellular carcinoma (Review).

    abstract::Hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC) is a global health problem that accounts for more than half of total liver cancer cases in developing countries. Despite the growing number of researches conducted, the molecular mechanism underlying the development of HCC remains elusive. Long non‑coding ...

    journal_title:International journal of oncology

    pub_type: 杂志文章,评审

    doi:10.3892/ijo.2019.4909

    authors: Zhang H,Chen X,Zhang J,Wang X,Chen H,Liu L,Liu S

    更新日期:2020-01-01 00:00:00

  • Reliability of a primary culture system to test cytotoxic drug activity in human-malignant melanoma.

    abstract::Optimal conditions have been defined to grow primary cultures of malignant melanoma suitable for in vitro pharmacological studies. A feasibility of primary cultures was observed in 60% of 62 clinical melanoma lymph node metastases. The neoplastic nature of the cells grown in culture, as assessed by the highly specific...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.6.619

    authors: Villa R,Zaffaroni N,Orlandi L,Costa A,Veronese S,Vaglini M,Silvestrini R

    更新日期:1992-11-01 00:00:00

  • Expression of microRNA-21 in non-small cell lung cancer tissue increases with disease progression and is likely caused by growth conditional changes during malignant transformation.

    abstract::MicroRNAs can govern up to hundred different mRNAs and are important regulators of gene expression programs in development and disease. We analyzed the expression of microRNA-21, one of the most common oncomirs, in non-small cell lung cancer (NSCLC). Using northern blots the microRNA-21 expression levels of NSCLC-deri...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2014.2272

    authors: Haigl B,Vanas V,Setinek U,Hegedus B,Gsur A,Sutterlüty-Fall H

    更新日期:2014-04-01 00:00:00

  • Breast cancer proteomics reveals a positive correlation between glyoxalase 1 expression and high tumor grade.

    abstract::Breast cancer is the neoplasia with the highest incidence in women worldwide. Proteomics approaches have accelerated the discovery of diagnostic and prognostic biomarkers. Here, we compared the proteomic profiles of breast tumors versus non-tumoral tissues in order to identify modul...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2012.1478

    authors: Fonseca-Sánchez MA,Rodríguez Cuevas S,Mendoza-Hernández G,Bautista-Piña V,Arechaga Ocampo E,Hidalgo Miranda A,Quintanar Jurado V,Marchat LA,Alvarez-Sánchez E,Pérez Plasencia C,López-Camarillo C

    更新日期:2012-08-01 00:00:00

  • A novel transcript variant of proteasome activator 28γ: Identification and function in oral cancer cells.

    abstract::Proteasome activator 28γ (PA28γ) binds to and activates the proteasome in an ATP-independent manner to promote mainly ubiquitin-independent protein degradation in cells. Previously, four transcript variants of PA28γ have been identified, which have been closely correlated with the progression of cancers. In the presen...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2015.2980

    authors: Xu X,Liu D,Ji N,Li T,Li L,Jiang L,Li J,Zhang P,Zeng X,Chen Q

    更新日期:2015-07-01 00:00:00

  • Genomic characterization of five commonly used endometrial cancer cell lines.

    abstract::Recently, the compilation of massive amounts of genetic and genomic information on a wide variety of human cancer types, collectively known as The Cancer Genome Atlas (TCGA), has revealed a wealth of descriptive classification schemes both within and between different types and sources of cancer. In endometrial cancer...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2020.5139

    authors: Devor EJ,Gonzalez-Bosquet J,Thiel KW,Leslie KK

    更新日期:2020-12-01 00:00:00

  • Identification of monoclonal B-cell populations in lymphoid infiltrates of lacrimal gland by rapid cycle polymerase chain-reaction.

    abstract::Lymphoid hyperplasia of lacrimal gland may be difficult to be differentiated from lymphomas on the basis of morphology and immunohistochemistry. The results of this study indicate that polymerase chain reaction should be employed for confirming the diagnosis of lymphoma in cases with histological and immunophenotypica...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.3.5.897

    authors: Leoncini L,Funto I,Lazzi S,Pacenti L,Polito E,Bartolomei A,Leccisotti A,Cintorino M,Tosi P

    更新日期:1993-11-01 00:00:00

  • Reversible dissociation of a tumor-cell surface protease-inhibitor complex.

    abstract::Tumour cell surfaces possess a cell surface protease (GB), which can be recognised by a cytoplasmic inhibitor protein prepared from cultured tumour cells. This enzyme inhibitor complex has been shown to be reversibly dissociated by 10-(4)M sodium dodecyl sulphate. Sections of frozen tumour tissue were used to provide ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.1.1.59

    authors: Steven F,Griffin M,Blakey D

    更新日期:1992-06-01 00:00:00

  • Transcriptome analysis of hepatitis B virus-associated small hepatocellular carcinoma by serial analysis of gene expression.

    abstract::Serial analysis of gene expression (SAGE) is a sequence-based tool that enables quantitative study of comprehensive gene expression profiles. In this study, we generated a SAGE library of hepatitis B virus (HBV)-associated small hepatocellular carcinoma (HCC) and compared it with libraries of normal liver and other or...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo_00000321

    authors: Kim JW,Lee SH,Park YS,Jeong SH,Kim N,Lee DH,Lee HS

    更新日期:2009-07-01 00:00:00

  • Screening of peptides which suppress the proliferation of transformed cells.

    abstract::We have carried out three rounds of screening tests using 239 synthetic tripeptides for the growth-inhibitory activity toward tumor cells and found that those having amino acid sequences of Pro-Thr-Trp or Glu-Arg-Pro effectively inhibit proliferation of transformed cells. These peptides could be the fundamental struct...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Hiwasa T,Soeda C,Takanohashi S,Kobayashi H,Suzuki A,Ueyama T,Ike Y

    更新日期:1996-01-01 00:00:00

  • Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells.

    abstract::An ETS family member, ETS Related Gene (ERG) is involved in the Ewing family of tumors as well as leukemias. Rearrangement of the ERG gene with the TMPRSS2 gene has been identified in the majority of prostate cancer patients. Additionally, overexpression of ERG is associated with unfavorable prognosis in prostate canc...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2011.1014

    authors: Fortson WS,Kayarthodi S,Fujimura Y,Xu H,Matthews R,Grizzle WE,Rao VN,Bhat GK,Reddy ES

    更新日期:2011-07-01 00:00:00

  • Galiximab (anti-CD80)-induced growth inhibition and prolongation of survival in vivo of B-NHL tumor xenografts and potentiation by the combination with fludarabine.

    abstract::Galiximab is a primatized monoclonal antibody that targets CD80 expressed on malignant B cells and is being studied in the clinic as a potential treatment for follicular NHL. We have recently reported that galiximab signals B-NHL cells in vitro and inhibits cell growth and sensitizes resistant tumor cells to apoptosis...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.2013.1986

    authors: Hariharan K,Chu P,Murphy T,Clanton D,Berquist L,Molina A,Ho SN,Vega MI,Bonavida B

    更新日期:2013-08-01 00:00:00

  • Overcoming the classical multidrug resistance phenotype by adenoviral delivery of anti-MDR1 short hairpin RNAs and ribozymes.

    abstract::Simultaneous resistance of cancer cells to multiple cytotoxic drugs, multidrug resistance (MDR), is the major limitation to the successful chemotherapeutic treatment of disseminated neoplasms. The 'classical' MDR phenotype is conferred by MDR1/P-glycoprotein (MDR1/P-gp) that is expressed in almost 50% of human cancers...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kaszubiak A,Holm PS,Lage H

    更新日期:2007-08-01 00:00:00

  • Predicting response to docetaxel neoadjuvant chemotherapy for advanced breast cancers through genome-wide gene expression profiling.

    abstract::Neoadjuvant chemotherapy with docetaxel for advanced breast cancer can improve the radicality for a subset of patients, but some patients suffer from severe adverse drug reactions without any benefit. To establish a method for predicting responses to docetaxel, we analyzed gene expression profiles of biopsy materials ...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Zembutsu H,Suzuki Y,Sasaki A,Tsunoda T,Okazaki M,Yoshimoto M,Hasegawa T,Hirata K,Nakamura Y

    更新日期:2009-02-01 00:00:00

  • Frequent silence of chromosome 9p, homozygous DOCK8, DMRT1 and DMRT3 deletion at 9p24.3 in squamous cell carcinoma of the lung.

    abstract::Chromosomal alterations are a major genomic force contributing to the development of lung cancer. We subjected 22 cases of squamous cell carcinoma of the lung (SCC) to whole-genome microarray-CGH (resolution, 1 Mb) to identify critical genetic landmarks that might be important mediators in the formation or progression...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:

    authors: Kang JU,Koo SH,Kwon KC,Park JW

    更新日期:2010-08-01 00:00:00

  • Antiangiogenic and antitumor effects of tranilast on mouse lung carcinoma cells.

    abstract::We examined the effects of tranilast on tumor angiogenesis, tumor growth and metastasis in the mouse Lewis lung carcinoma and C57BL mouse system. Tranilast significantly reduced the dense capillary network induced by Lewis lung cancer cells in a mouse dorsal air sac angiogenesis model. Intraperitoneal administration o...

    journal_title:International journal of oncology

    pub_type: 杂志文章

    doi:10.3892/ijo.17.6.1151

    authors: Yatsunami J,Aoki S,Fukuno Y,Kikuchi Y,Kawashima M,Hayashi SI

    更新日期:2000-12-01 00:00:00