Cross-regulation between FOXA1 and ErbB2 signaling in estrogen receptor-negative breast cancer.

Neoplasia : an International Journal for Oncology Research
Ali NaderiDennis H Dowhan

Abstract

Molecular apocrine is a subtype of estrogen receptor-negative (ER.) breast cancer, which is characterized by a steroid-response gene signature that includes androgen receptor, FOXA1, and a high frequency of ErbB2 overexpression. In this study, we demonstrate that there is a strong association between the overexpression of FOXA1 and ErbB2 in ER- breast tumors. This has led us to identify a cross-regulation network between FOXA1 and ErbB2 signaling in ER- breast cancer. We present two mechanisms to explain the association between FOXA1 and ErbB2 overexpression in molecular apocrine cells. In one process, ErbB2 signaling genes CREB1 and c-Fos regulate FOXA1 transcription, and in another process, AP2α regulates the expression of both FOXA1 and ErbB2. Moreover, we demonstrate that FOXA1, in turn, regulates the transcription of ErbB2 signaling genes. This includes a core gene signature that is shared across two molecular apocrine cell lines. Importantly, the most upregulated (RELB) and downregulated (PAK1) genes in this signature are direct FOXA1 targets. Our data suggest that FOXA1 acts as a dual-function transcription factor and the repressive function of FOXA1 on RELB can be explained by the recruitment of its binding partner core...Continue Reading

Citations

Jun 22, 2014·Endocrine-related Cancer·Keely M McNamaraWayne D Tilley
Sep 29, 2020·Frontiers in Endocrinology·Mengyao ChenFuming Qiu
Nov 30, 2012·Chromosoma·Elisa FioritoAntoni Hurtado
Aug 13, 2013·Breast Cancer Research and Treatment·Yan-Mei WuWei-Qiang Zheng
Jul 9, 2014·Endocrine-related Cancer·Gerard A TarulliTheresa E Hickey
Oct 21, 2016·PloS One·Cortney L Lawrence, Albert S Baldwin
Jun 8, 2018·Biomedicines·Matthew Tegowski, Albert Baldwin
Mar 2, 2019·Critical Reviews in Clinical Laboratory Sciences·Stella K Vasiliou, Eleftherios P Diamandis
Feb 20, 2019·Molecular Biology Reports·Reza MohammadiMehdi Moghanibashi
Dec 1, 2020·The Science of the Total Environment·Mei HaChangjiang Liu
Jun 22, 2019·Biochemical and Biophysical Research Communications·Xiuyu WangRan Du
May 14, 2021·NPJ Breast Cancer·Steven P AngusGary L Johnson
Oct 13, 2021·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Bin LiRong Zhong

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