Journal article
A TFAP2C Gene Signature is Predictive of Outcome in HER2-positive Breast Cancer
Molecular cancer research, Vol.18(1), pp.46-56
01/2020
DOI: 10.1158/1541-7786.MCR-19-0359
PMID: 31619506
Abstract
The AP-2γ transcription factor, encoded by the
TFAP2C
gene, regulates the expression of estrogen receptor-alpha (ERα) and other genes associated with hormone response in luminal breast cancer. Little is known about the role of AP-2γ in other breast cancer subtypes. A subset of HER2+ breast cancers with amplification of the
TFAP2C
gene locus becomes addicted to AP-2γ. Herein we sought to define AP-2γ gene targets in HER2+ breast cancer and identify genes accounting for physiologic effects of growth and invasiveness regulated by AP-2γ. Comparing HER2+ cell lines that demonstrated differential response to growth and invasiveness with knockdown of
TFAP2C
, we identified a set of 68 differentially expressed target genes.
CDH5
and
CDKN1A
were among the genes differentially regulated by AP-2γ and that contributed to growth and invasiveness. Pathway analysis implicated the
MAPK13
/p38δ and retinoic acid regulatory nodes, which were confirmed to display divergent responses in different HER2+ cancer lines. To confirm the clinical relevance of the genes identified, the AP-2γ gene signature was found to be highly predictive of outcome in HER2+ breast cancer patients. We conclude that AP-2γ regulates a set of genes in HER2+ breast cancer that drive cancer growth and invasiveness. The AP-2γ gene signature predicts outcome of patients with HER2+ breast cancer and pathway analysis predicts that subsets of patients will respond to drugs that target the MAPK or retinoic acid pathways.
Details
- Title: Subtitle
- A TFAP2C Gene Signature is Predictive of Outcome in HER2-positive Breast Cancer
- Creators
- Vincent T Wu - University of IowaBoris Kiriazov - University of IowaKelsey E Koch - University of IowaVivian W Gu - University of IowaAnna C Beck - University of IowaNicholas Borcherding - University of IowaTiandao Li - University of IowaPeter Addo - University of IowaZachary J Wehrspan - University of IowaWeizhou Zhang - University of FloridaTerry A Braun - University of IowaBartley J Brown - University of IowaVimla Band - University of Nebraska Medical CenterHamid Band - University of Nebraska Medical CenterMikhail V Kulak - University of IowaRonald J Weigel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular cancer research, Vol.18(1), pp.46-56
- DOI
- 10.1158/1541-7786.MCR-19-0359
- PMID
- 31619506
- NLM abbreviation
- Mol Cancer Res
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: R01CA183702, T32CA148062; DOI: 10.13039/100000002, name: NIH, award: P30CA08686218S6; DOI: 10.13039/100000002, name: NIH, award: T32CA148062
- Language
- English
- Date published
- 01/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Dermatology; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Radiation Oncology; Biochemistry and Molecular Biology
- Record Identifier
- 9984197159702771
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