Inhibition of RelB Synthesis by ERa Signalling Controls the Shift in Breast Cancer Cell Phenotypes

Gail E. Sonenshein, Ph.D.
Boston University School of Medicine
P01ES011624

RelB is a widely expressed protein involved in the regulation of genes involved in cell-to-cell interaction, intercellular communication, cell recruitment, spreading of pathogenic signals, cell apoptosis, and initiation or acceleration of tumorigenesis. RelB complexes are often found in mouse mammary tumors, but little is known about the function of RelB in relation to human breast cancer.

NIEHS grantee Gail Sonenshein at the Boston University School of Medicine reports in the April issue of Nature Cell Biology research findings that connect RelB with the estrogen receptor alpha (ERa). In invasive ERa-negative breast cancer cells, her team found active synthesis of RelB; however, ERa signaling led to an inhibition of RelB synthesis, leading to an inverse correlation between RelB and ERa gene expression in human breast cancer tissues and cell lines. Additional studies demonstrated that RelB promotes a more invasive type of ERa-negative breast cancer cells.

This work provides further understanding of the role of RelB in human breast cancer and indicates that inhibition of RelB synthesis represents a mechanism by which ERa can control the shift of epithelial cells to a more invasive phenotype. The authors conclude that further studies are warranted to determine if RelB is useful as a marker or in therapeutic approaches for the detection and treatment of metastatic breast cancer.

Citation: Wang X, Belguise K, Kersual N, Kirsch KH, Mineva ND, Galtier F, Chalbos D, Sonenshein GE. Oestrogen signalling inhibits invasive phenotype by repressing RelB and its target BCL2. Nat Cell Biol. 2007 Apr;9(4):470-8.