Figure 1. The acquired resistance to BETi was through the stabilization of MYCN protein due to activated ERK1/2 in NB cells. (IMAGE)

_Tokyo Medical and Dental University

Figure 1. The acquired resistance to BETi was through the stabilization of MYCN protein due to activated ERK1/2 in NB cells.

Caption

(A) Establishment of BETi-resistant IMR-32 (IMR-32-JQ1R) cells. Dose-response curve for cell viability of IMR-32 and IMR-32-JQ1R cells treated with different concentrations of JQ1 for 48 h. (B) Western blot analysis of MYCN expression in IMR-32 and IMR-32-JQ1R cells after treatment with JQ1 at 0, 0.25, 0.50, or 1.0 µmol/L. (C) Western blot analysis showed increased expression of p-MYCN (S62) and p-ERK1/2 in IMR-32-JQ1R cells. (D) Cycloheximide (CHX) chase assay. The half-life of MYCN protein was longer in IMR-32-JQ1R cells than in IMR-32 cells. (E) Ubiquitinated MYCN was reduced in IMR-32-JQ1R cells compared with in IMR-32 cells. (F) miR-3140-3p efficiently downregulated MYCN expression by directly targeting the MAP3K3-ERK1/2 pathway in addition to BRD4 suppression.

Credit

Department of Molecular Cytogenetics, TMDU

Usage Restrictions

None

License

Licensed content

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.