@article{c9d0a6742984403f88cb38431ae421e9,
title = "HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer",
abstract = "HER2/Neu is overexpressed in 25-30% of all human breast cancers as a result of both gene amplification and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6-8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neu-overexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These findings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins affecting its regulation are appropriate therapeutic targets.",
keywords = "Breast cancer, Ets transcription factor, HER2/Neu, PEA3",
author = "Benz, {Christopher C.} and O'Hagan, {Ronan C.} and Birgit Richter and Scott, {Gary K.} and Chang, {Chuan Hsiung} and Xiaohui Xiong and Karen Chew and Ljung, {Britt Marie} and Susan Edgerton and Ann Thor and Hassell, {John A.}",
note = "Funding Information: We thank Laura Hastings and Jane Barrett for technical assistance, and Michael Rudnicki and Richard Tozer for their comments on the manuscript. We also thank Bill Muller for providing plasmid DNAs bearing the HER2/neu cDNAs. This work was supported in part by grants to JAH from the National Cancer Institute of Canada and the Medical Research Council of Canada, and by grants to CCB from the Janet Landfear Memorial Fund, the Hazel P Munroe Memorial Fund, and the NIH (CA44768, CA36773 and CA58207). R O{\textquoteright}Hagan was supported by a 1967 Science and Engineering Scholarship from the Natural Sciences and Engineering Research Council of Canada, and was a recipient of a 1996 B-M Squibb/ American Association of Cancer Research award in recognition of his predoctoral work on this project.",
year = "1997",
doi = "10.1038/sj.onc.1201331",
language = "English",
volume = "15",
pages = "1513--1525",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Springer Nature",
number = "13",
}