Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2022 Apr 1;24:23. doi: 10.1186/s13058-022-01521-3

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

PMC Copyright notice

Fig. 2 — SHP2 confers resistance to PI3K inhibition upon overexpression and long-term PI3K inhibitor exposure. a MCF7 cells overexpressing wild type SHP2 (SHP2-WT) are resistant to BYL719 (5 μM) treatment. MCF7-pCMV-EGFP (EGFP) cells serve as control. Quantification of crystal violet staining intensity of three colony formation experiments is shown. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. b Biochemical analysis by western blot of the effect on PI3K and MAPK signaling in cells overexpressing SHP2. Significant differences (p ≤ 0.05) in p-SHP2, SHP2 and p-ERK in comparison to the untreated condition in parental cells are marked with an *. BYL719: 5 μM. c Long-term treatment with BYL719 of MCF7, T47D and MDA-MB-453 cells (for 38, 50 and 50 days, respectively) results in outgrowth of resistant clones. BYL719/SHP099 combination treatment prevents outgrowth of BYL719 resistant clones. Vehicle (UT) and SHP099-only treated cells serve as control. BYL719: 5 μM (MCF7), 2 μM (T47D) and 1 μM (MDA-MB-453). SHP099: 5 μM (MCF7 and MDA-MB-453), 10 μM (T47D). d Biochemical analysis of SHP2, PI3K and MAPK signaling of ten BYL719 resistant T47D clones. Parental cells were treated with BYL719 for 24 h. BYL719: 2 μM. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *. e Colony formation (top) and quantification of three colony formation experiments (bottom) of two BYL719-resistant T47D clones that are co-treated with BYL719 and SHP099. Significance between indicated conditions was calculated by one-way ANOVA. ****p ≤ 0.0001. BYL719: 2 μM. SHP099: 10 μM. f Biochemical effects of BYL719 (2 μM) and SHP099 (10 μM) combination treatment on PI3K and MAPK signaling in BYL719-resistant T47D clone #1. Significant differences (p ≤ 0.05) in signaling in comparison to the untreated condition in parental cells are marked with an *