Regulation of MDR1 gene expression in multidrug-resistant cancer cells is independent from YB-1

Kaszubiak, Alexander; Kupstat, Annette; Müller, Ursula; Hausmann, Romy; Holm, Per Sonne; Lage, Hermann

doi:10.1016/j.bbrc.2007.03.145

Cited by 21 publications

(14 citation statements)

References 26 publications

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“…To verify the specificity of Ad-Delo3-RGD, we used a tetracycline-inducible anti-YB-1 shRNA-expressing cell variant EPG85-257RDB/tetR/YB-1. 16 YB-1 knock-down in EPG85-257RDB/tetR/YB-1 led to reduced YB-1 mRNA and protein levels as reported before. This inducible system allowed us to verify a significant YB-1 dependency of Ad-Delo3-RGD replication (Figure 2).…”

Section: Discussionsupporting

confidence: 78%

“…Knock down of YB-1 with shRNA, which was verified by western blot analysis 16 and immunohistochemistry (data not shown) decreased significantly the viral replication at one MOI by 69.9% and at five MOI by 57.1%, showing the high YB-1 dependency of Ad-Delo3-RGD (Figure 2). Similar results were YB-1 mediated virotherapy E Rognoni et al obtained using two additional YB-1-dependent oncolytic adenoviruses dl520 21 and XVir03 22 (data not shown).…”

Section: Yb-1 Dependency Of Ad-delo3-rgdmentioning

confidence: 75%

“…Establishment and characterization of the tetracycline-inducible anti-YB-1 shRNA-expressing cell variants EPG85-257RDB/tetR/ YB-1 was described earlier. 16 …”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

“…For quantitative viral replication analysis, a real-time PCR protocol was applied using a LightCycler instrument and SYBR-Green fluorescent dye (Roche Diagnostics, Mannheim, Germany), as described earlier. 16 Specific primers used for amplification of adenoviral DNA were: Hexon-fw 5 0 -acctttgactcttctgt-3 0 ; Hexon-rev 5 0 -gctagcatttgtaccag-3 0 . Cycling conditions were as follows: initial enzyme activation at 95 1C for 10 min, followed by 35 Cytopathic effect assay For determination of virus-mediated cell killing, cells were seeded in 12-well plates at a density of 1 Â 10 5 per well.…”

Section: Adenoviral Vectorsmentioning

confidence: 99%

“…15 To address the YB-1 dependency of Ad-Delo3-RGD, we used an established tetracycline-inducible anti-YB-1 shRNA-expressing cell variant EPG85-257RDB/tetR/ YB-1. 16 The drug-resistant cell line EPG85-257RDB is characterized by its high CAR expression and the presence of nuclear YB-1 (because of cultivation in the presence of the cytostatic drug daunorubicin). Thus, this TetON regulatable expression system allows us to measure adenoviral replication by real-time PCR in the absence of YB-1 expression.…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-based virotherapy enabled by cellular YB-1 expression in vitro and in vivo

et al. 2009

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We have earlier described the oncolytic adenovirus vector dl520 that was rendered cancer-specific by deletion of the transactivation domain CR3 of the adenoviral E1A13S protein; this deletion causes antitumor activity in drug-resistant cells displaying nuclear YB-1 expression. We hypothesized that the anticancer activity of dl520 could be further improved by introducing the RGD motif in the fiber knob and by deletion of the adenoviral E1B19K protein (Ad-Delo3-RGD). In this study, the in vitro and in vivo antitumor activity of Ad-Delo3-RGD was investigated focussing on two pancreatic cancer cell lines MiaPaCa-2 and BxPC3 alone and in combination with cytotoxic drugs. Furthermore, luciferin-based bioluminescence imaging was established to study the therapeutic response in vivo. In addition, to confirm the specificity of Ad-Delo3-RGD for YB-1 a tetracycline-inducible anti-YB-1 shRNA-expressing cell variant EPG85-257RDB/tetR/YB-1 was used. This TetON regulatable expression system allows us to measure adenoviral replication by real-time PCR in the absence of YB-1 expression. The results confirmed the YB-1 dependency of Ad-Delo3-RGD and showed that Ad-Delo3-RGD has potent activity against human pancreatic cancer cells in vitro and in vivo, which was augmented by the addition of paclitaxel. However, although high replication capacity was measured in vitro and in vivo, complete tumor regression was not achieved, indicating the need for further improvements to treat pancreatic cancer effectively.

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Section: Discussionsupporting

confidence: 78%

Section: Yb-1 Dependency Of Ad-delo3-rgdmentioning

confidence: 75%

“…Establishment and characterization of the tetracycline-inducible anti-YB-1 shRNA-expressing cell variants EPG85-257RDB/tetR/ YB-1 was described earlier. 16 …”

Section: Cell Lines and Culture Conditionsmentioning

confidence: 99%

Section: Adenoviral Vectorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adenovirus-based virotherapy enabled by cellular YB-1 expression in vitro and in vivo

et al. 2009

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A novel EGR‐1 dependent mechanism for YB‐1 modulation of paclitaxel response in a triple negative breast cancer cell line

Lasham

Mehta

Fitzgerald

et al. 2016

Intl Journal of Cancer

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Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Because a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required. One protein shown to be involved in drug resistance is Y-box binding protein 1 (YB-1). High levels of YB-1 have previously been associated with resistance to PTX in TNBCs. In this study, we aimed to determine mechanisms by which YB-1 confers PTX resistance. We generated isogenic TNBC cell lines that differed by YB-1 levels and treated these with PTX. Using microarray analysis, we identified EGR1 as a potential target of YB-1. We found that low EGR1 mRNA levels are associated with poor breast cancer patient prognosis, and that EGR1 and YBX1 mRNA expression was inversely correlated in a TNBC line and in a proportion of TNBC tumours. Reducing the levels of EGR1 caused TNBC cells to become more resistant to PTX. Given that PTX targets cycling cells, we propose a model whereby high YB-1 levels in some TNBC cells can lead to reduced levels of EGR1, which in turn promotes slow cell cycling and resistance to PTX. Therefore YB-1 and EGR1 levels are biologically linked and may provide a biomarker for TNBC response to PTX.

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YB‐1 protein: functions and regulation

2013

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The Y-box binding protein 1 (YB-1, YBX1) is a member of the family of DNA- and RNA-binding proteins with an evolutionarily ancient and conserved cold shock domain. It falls into a group of intrinsically disordered proteins that do not follow the classical rule 'one protein-one function' but introduce a novel principle stating that a disordered structure suggests many functions. YB-1 participates in a wide variety of DNA/RNA-dependent events, including DNA reparation, pre-mRNA transcription and splicing, mRNA packaging, and regulation of mRNA stability and translation. At the cell level, the multiple activities of YB-1 are manifested as its involvement in cell proliferation and differentiation, stress response, and malignant cell transformation. WIREs RNA 2014, 5:95-110. doi: 10.1002/wrna.1200 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

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Regulation of MDR1 gene expression in multidrug-resistant cancer cells is independent from YB-1

Cited by 21 publications

References 26 publications

Adenovirus-based virotherapy enabled by cellular YB-1 expression in vitro and in vivo

Adenovirus-based virotherapy enabled by cellular YB-1 expression in vitro and in vivo

A novel EGR‐1 dependent mechanism for YB‐1 modulation of paclitaxel response in a triple negative breast cancer cell line

YB‐1 protein: functions and regulation

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