Summary of Study ST002748
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001711. The data can be accessed directly via it's Project DOI: 10.21228/M8JD9D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002748 |
| Study Title | HER2 overexpression initiates breast tumorigenesis non-cell autonomously by inducing oxidative stress in the tissue microenvironment |
| Study Summary | HER2 is a driver oncogene overexpressed in the majority of premalignant breast tumors known as ductal carcinoma in situ (DCIS). Due to their stemness features, breast cancer stem cells (BCSC) are considered the main drivers of breast tumor initiation and progression. Here, we used clinical samples and mouse models of HER2+ breast tumorigenesis to demonstrate that neither BCSCs nor their cell-of-origin express HER2/Neu in early-stage breast tumors. Instead, our results demonstrate that Neu overexpression results in the transformation of BCSCs in a non-cell autonomous manner via triggering DNA damage and somatic mutagenesis in their Neu-negative cell-of-origin. This is caused by the increased oxidative stress in the tissue microenvironment generated by altered energy metabolism and increased reactive oxygen species level in Neu-overexpressing mammary ducts. Therefore, our findings illustrate a previously unrecognized mechanism of HER2-induced breast tumor initiation, which may have an impact on future preventive treatments for patients with HER2+ DCIS. |
| Institute | The University of Manchester |
| Department | Manchester Breast Centre |
| Laboratory | Ahmet Ucar Lab |
| Last Name | Ucar |
| First Name | Ahmet |
| Address | Oxford Road, Manchester, M13 9PL, UK. |
| ahmet.ucar@manchester.ac.uk | |
| Phone | +44 (0)161 3067116 |
| Submit Date | 2023-06-26 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | wiff |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-07-10 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004458 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo-Fisher Ultimate 3000 HPLC |
| Column | Agilent Poroshell 120 HILIC-Z |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6600 QTOF |
| Ion Mode | NEGATIVE |
| Units | Peak area |
Chromatography:
| Chromatography ID: | CH003347 |
| Chromatography Summary: | Liquid chromatography-mass spectrometry analysis was performed using a Thermo-Fisher Ultimate 3000 HPLC system consisting of an HPG-3400RS high pressure gradient pump, TCC 3000SD column compartment and WPS 3000 Autosampler, coupled to a SCIEX 6600 TripleTOF Q-TOF mass spectrometer with TurboV ion source. The system was controlled by SCIEX Analyst 1.7.1, DCMS Link and Chromeleon Xpress software. |
| Instrument Name: | Thermo-Fisher Ultimate 3000 HPLC |
| Column Name: | Agilent Poroshell 120 HILIC-Z |
| Column Temperature: | 40 |
| Flow Gradient: | flow rate of 0.25 ml/min, starting at 96 % B for 2 minutes, ramping to 65 % B over 20 min, hold at 65 % B for 2 min, then back to 96 % B |
| Flow Rate: | 0.25 ml/min |
| Solvent A: | 100% water; 10 mM ammonium acetate adjusted to pH 9 with ammonium hydroxide and 20 µM medronic acid |
| Solvent B: | 85% acetonitrile/15% water; 10 mM ammonium acetate adjusted to pH 9 with ammonium hydroxide and 20 µM medronic acid |
| Chromatography Type: | HILIC |
