HER4 selectively coregulates estrogen stimulated genes associated with breast tumor cell proliferation

Biochemical and Biophysical Research Communications
Wen Han, Frank E Jones

Abstract

The EGFR-family member HER4 undergoes regulated intramembrane proteolysis (RIP) to generate an intracellular domain (4ICD) that functions as a transcriptional coactivator. Accordingly, 4ICD coactivates the estrogen receptor (ER) and associates with ER at target gene promoters in breast tumor cells. However, the extent of 4ICD coactivation of ER and the functional significance of the 4ICD/ER transcriptional complex is unclear. To identify 4ICD coactivated genes we performed a microarray gene expression analysis of β-estradiol treated cells comparing control MCF-7 breast cancer cells to MCF-7 cells where HER4 expression was stably suppressed using a shRNA. In the MCF-7 cell line, β-estradiol significantly stimulated or repressed by 2-fold or more 726 or 53 genes, respectively. Significantly, HER4/4ICD was an obligate coactivator for 277 or 38% of the β-estradiol stimulated genes. Ingenuity Pathway Analysis of β-estradiol regulated genes identified significant associations with multiple cellular functions regulating cellular growth and proliferation, cell cycle progression, cancer metastasis, decreased hypoplasia, tumor cell migration, apoptotic resistance of tumor cells, and increased transcription. Genes coactivated by 4ICD disp...Continue Reading

References

May 14, 2003·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Valerie-Jeanne BardouGary M Clark
Nov 10, 2004·The Journal of Cell Biology·Christopher C WilliamsFrank E Jones
Jan 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Paul LabhartCarolyn L Smith
May 6, 2008·Journal of Mammary Gland Biology and Neoplasia·Maria SundvallKlaus Elenius
Jun 12, 2012·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Urszula M DomanskaAnnemiek M E Walenkamp
Jun 27, 2012·Nature Reviews. Endocrinology·David M Lonard, Bert W O'Malley

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