Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance

Yabuki, Nami; Sakata, Kiyoaki; Yamasaki, Tomoaki; Terashima, Hiromichi; Mio, Toshiyuki; Miyazaki, Youko; Fujii, Toshihiko; Kitada, Koji

doi:10.1016/j.cancergencyto.2006.07.020

Cited by 68 publications

(49 citation statements)

References 23 publications

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“…Gene amplification is also a potential mechanism for increased ABCB1 transcription, given previously published findings using a variety of drug-resistant cancer cell lines. [20][21][22][23] No ABCB1 gene amplification could be detected in MCF-7 EPI and MCF-7 TAX-2 cells (relative to MCF-7 CC cells) when assessed by Q-PCR experiments using genomic DNA and ABCB1-specific primers (Figure 2). This lack of ABCB1 amplification was further confirmed by FISH studies (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…A region with strong hypomethylation induced by selection for drug resistance spans CpG sites 49-66. Shared valleys of hypomethylation in drug-resistant and Azatreated cells span CpG sites [19][20][21][22], which correspond to the consensus Inr site, a site adjacent to the transcription start site (Table 3), and CpG sites 32-44 implicated in the regulation of ABCB1 expression by p53 (Table 4). Aza treatment did not result in dramatic reduction in the methylation of CpG sites 49-66 (Figure 5f).…”

Section: Discussionmentioning

confidence: 99%

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The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance

et al. 2010

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Induced expression of the Abcb1 drug transporter often occurs in tumors in response to chemotherapy. The role that epigenetic modifications within the ABCB1 promoter play in Abcb1 expression remains unclear. We selected MCF-7 cells for survival in increasing doses of chemotherapy drugs, and assessed the methylation status of 66 CpG sites within the ABCB1 promoter preceding, accompanying and following the onset of drug resistance. Increased ABCB1 transcript expression coincident with acquisition of resistance to epirubicin or paclitaxel was temporally associated with hypomethylation of the ABCB1 downstream promoter in the absence of gene amplifications or changes in mRNA stability. Treatment of control MCF-7 cells with demethylating and/or acetylating agents increased ABCB1 transcript expression. In addition to broad promoter hypomethylation, dramatic reductions in the methylation of specific CpG sites within the promoter were observed, suggesting that these sites may play a predominant role in transcriptional activation through promoter hypomethylation. Furthermore, our data suggest that allele-specific reductions in ABCB1 promoter methylation regulate promoter usage within paclitaxel-resistant cells. This study provides strong evidence that changes in ABCB1 promoter methylation, ABCB1 promoter usage and ABCB1 transcript expression can be temporally and causally correlated with the acquisition of drug resistance in breast tumor cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance

et al. 2010

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“…- have shown that acquired drug-resistant cell lines have amplification of the ABCB1 chromosome region (24). Therefore, prior palliative chemotherapy history could affect the expression of ABCB1, resulting in the development of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Association of the ABCB1 3435C>T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy

Chung¹

2009

Oncol Rep

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Abstract.We evaluated the frequency of ABCB1 polymorphisms (2677G/T>A and 3435C>T) and studied the association between the polymorphisms and clinical outcomes of paclitaxel-based chemotherapy in advanced gastric cancer patients. This study was performed in 43 gastric cancer patients and a control group consisting of 118 healthy volunteers. Patients were treated with paclitaxel combined with an infusional 5-fluorouracil and low-dose leucovorin. Genomic DNA from peripheral blood mononuclear cells was used to determine ABCB1 polymorphisms by direct sequencing. Genotypes were investigated for their association with survival and toxicity. The ABCB1 3435 C allele was more frequent in gastric cancer patients than healthy volunteers (p<0.001). The 2677G>T/A and 3435C>T polymorphisms were independent factors associated with shorter progression-free survival (PFS) (p=0.024, p=0.001, respectively). In combined analysis of 2677 and 3435 polymorphisms, the 3435C>T polymorphism was an independent factor for poor PFS (p=0.01). The 3435CT and TT genotypes were associated with mucositis (p=0.04), and the variant genotypes at 2677 loci were associated with diarrhea (p=0.034). Our data suggest that the ABCB1 polymorphism at 3435 is associated with clinical outcomes after paclitaxel-based combined chemotherapy in advanced gastric cancer patients.

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“…Mdr1 gene amplification can be due to the amplification of the q21-q22 region of chromosome 7 where the mdr1 gene is located or the formation of double minute chromosomes that carry the mdr1 gene. Amplification of region on chromosome 7 has been reported in Taxol-selected lung cancer cells (23), vincristine-selected leukemia (24) and Dox-selected prostate carcinoma (25). Amplification associated with double minute chromosome has been found in Dox and vinblastine-resistance KB carcinoma cells (15).…”

Section: Discussionmentioning

confidence: 99%

Facilitation of drug resistance development by γ-irradiation in human cancer cells

Kwok¹

2009

Oncol Rep

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Abstract. Hepatocellular carcinoma HepG2 cells (G cells)were subjected to selection first with Á-radiation and then doxorubicin (Dox). The radiation treatment consisted of 2 Gy for 10 days (G2) or 10 Gy for 2 days (G10) and the Dox treatment was continuous exposure for up to 10 μM. Compared with respective parental G, G2, G10 cells, the Doxselected cells showed mdr1 amplification/P-glycoprotein overexpression, Dox resistance and also less intracellular Dox accumulation. Verapamil reversed the drug resistance and increased the Dox accumulation in all cells. Decay in drug resistance and reduction in mdr1 amplification/P-glycoprotein overexpression were observed in the Dox-selected cells culturing in Dox-free condition. Among the Dox-selected cells, G2R cells showed the highest levels of drug resistance, mdr1 amplification, but the least resistance decay. Results from the study indicate the possible influence of radiation treatment on the development of drug resistance in cancer cells and it may even lead to a highly resistant phenotype.

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Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance

Cited by 68 publications

References 23 publications

The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance

The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance

Association of the ABCB1 3435C>T polymorphism and treatment outcomes in advanced gastric cancer patients treated with paclitaxel-based chemotherapy

Facilitation of drug resistance development by γ-irradiation in human cancer cells

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