Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells

Authors

Victor Okoh, Department of Environmental and Occupational Health, Florida International UniversityFollow
N. A. Garba, University of Arkansas
Jayanta K. Das, Department of Environmental & Occupational Health, Florida International UniversityFollow
Alok Deoraj, Department of Environmental and Occupational Health, Florida International UniversityFollow
K. P. Singh, Texas Tech University
S. Sarkar, UTMB, Galveston
Quentin Felty, Department of Environmental & Occupational Health, Florida International UniversityFollow
Changwon Yoo, Department of Biostatistics, Florida International UniversityFollow
R. M. Jackson, VA Medical Center
Deodutta Roy, Department of Environmental & Occupational Health, Florida International UniversityFollow

Date of this Version

10-22-2014

Document Type

Article

Abstract

Background:

17β-Oestradiol (E2)-induced reactive oxygen species (ROS) have been implicated in regulating the growth of breast cancer cells. However, the underlying mechanism of this is not clear. Here we show how ROS through a novel redox signalling pathway involving nuclear respiratory factor-1 (NRF-1) and p27 contribute to E2-induced growth of MCF-7 breast cancer cells.

Methods:

Chromatin immunoprecipitation, qPCR, mass spectrometry, redox western blot, colony formation, cell proliferation, ROS assay, and immunofluorescence microscopy were used to study the role of NRF-1.

Results:

The major novel finding of this study is the demonstration of oxidative modification of phosphatases PTEN and CDC25A by E2-generated ROS along with the subsequent activation of AKT and ERK pathways that culminated in the activation of NRF-1 leading to the upregulation of cell cycle genes. 17β-Oestradiol-induced ROS by influencing nuclear proteins p27 and Jab1 also contributed to the growth of MCF-7 cells.

Conclusions:

Taken together, our results present evidence in the support of E2-induced ROS-mediated AKT signalling leading to the activation of NRF-1-regulated cell cycle genes as well as the impairment of p27 activity, which is presumably necessary for the growth of MCF-7 cells. These observations are important because they provide a new paradigm by which oestrogen may contribute to the growth of breast cancer.

Comments

Originally published in the British Journal of Cancer.

Identifier

FIDC006493

Rights

by-nc-sa

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

Recommended Citation

Okoh, Victor; Garba, N. A.; Das, Jayanta K.; Deoraj, Alok; Singh, K. P.; Sarkar, S.; Felty, Quentin; Yoo, Changwon; Jackson, R. M.; and Roy, Deodutta, "Redox signalling to nuclear regulatory proteins by reactive oxygen species contributes to oestrogen-induced growth of breast cancer cells" (2014). Environmental Health Sciences. 10.
https://digitalcommons.fiu.edu/eoh_fac/10