Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

National Institute of Environmental Health Sciences

Use this QR code to view the newest version of this document
Use this QR code to view the newest version of this document

Your Environment. Your Health.

Publication Detail

Title: Roles of Small GTPases in Acquired Tamoxifen Resistance in MCF-7 Cells Revealed by Targeted, Quantitative Proteomic Analysis.

Authors: Huang, Ming; Wang, Yinsheng

Published In Anal Chem, (2018 Dec 18)

Abstract: Development of tamoxifen resistance remains a tremendous challenge for the treatment of estrogen-receptor (ER)-positive breast cancer. Small GTPases of the Ras superfamily play crucial roles in intracellular trafficking and cell signaling, and aberrant small-GTPase signaling is implicated in many types of cancer. In this study, we employed a targeted, quantitative proteomic approach that relies on stable-isotope labeling by amino acids in cell culture (SILAC), gel fractionation, and scheduled multiple-reaction-monitoring (MRM) analysis, to assess the differential expression of small GTPases in MCF-7 and the paired tamoxifen-resistant breast cancer cells. The method displayed superior sensitivity and reproducibility over the shotgun-proteomic approach, and it facilitated the quantification of 96 small GTPases. Among them, 13 and 10 proteins were significantly down- and up-regulated (with >1.5-fold change), respectively, in the tamoxifen-resistant line relative to in the parental line. In particular, we observed a significant down-regulation of RAB31 in tamoxifen-resistant cells, which, in combination with bioinformatic analysis and downstream validation experiments, supported a role for RAB31 in tamoxifen resistance in ER-positive breast-cancer cells. Together, our results demonstrated that the targeted proteomic method constituted a powerful approach for revealing the role of small GTPases in therapeutic resistance.

PubMed ID: 30431262 Exiting the NIEHS site

MeSH Terms: Biomarkers, Tumor/metabolism; Breast Neoplasms/metabolism; Breast Neoplasms/pathology; Chromatography, High Pressure Liquid; Down-Regulation/drug effects; Drug Resistance, Neoplasm/genetics*; Female; Gene Expression Regulation, Neoplastic/drug effects*; Humans; Isotope Labeling; MCF-7 Cells; Mass Spectrometry; Monomeric GTP-Binding Proteins/metabolism*; Proteomics*; Tamoxifen/pharmacology*; Up-Regulation/drug effects; rab GTP-Binding Proteins/analysis; rab GTP-Binding Proteins/chemistry; rab GTP-Binding Proteins/metabolism

Back
to Top