Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells - Archive ouverte HAL Access content directly
Journal Articles Frontiers in Pharmacology Year : 2020

Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells

(1, 2) , (1) , (3) , (1, 2) , (3) , (2) , (3) , (1, 2)
1
2
3

Abstract

Exposure to bisphenol A (BPA), one of the most widespread endocrine disruptors present in our environment, has been associated with the recent increased prevalence and severity of several diseases such as diabetes, obesity, autism, reproductive and neurological defects, oral diseases, and cancers such as breast tumors. BPA is suspected to act through genomic and non-genomic pathways. However, its precise molecular mechanisms are still largely unknown. Our goal was to identify and characterize a new molecular target of BPA in breast cancer cells in order to better understand how this compound may affect breast tumor growth and development. By using in vitro (MCF-7, T47D, Hs578t, and MDA-MB231 cell lines) and in vivo models, we demonstrated that PKD1 is a functional non-genomic target of BPA. PKD1 specifically mediates BPAinduced cell proliferation, clonogenicity, and anchorage-independent growth of breast tumor cells. Additionally, low-doses of BPA (≤10 −8 M) induced the phosphorylation of PKD1, a key signature of its activation state. Moreover, PKD1 overexpression increased the growth of BPA-exposed breast tumor xenografts in vivo in athymic female Swiss nude (Foxn1 nu/nu) mice. These findings further our understanding of the molecular mechanisms of BPA. By defining PKD1 as a functional target of BPA in breast cancer cell proliferation and tumor development, they provide new insights into the pathogenesis related to the exposure to BPA and other endocrine disruptors acting similarly.
Fichier principal
Vignette du fichier
fphar-10-01683.pdf (2.88 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

inserm-03033637 , version 1 (01-12-2020)

Identifiers

Cite

Messaouda Merzoug-Larabi, Ilige Youssef, Ai Thu Bui, Christine Legay, Sophia Loiodice, et al.. Protein Kinase D1 (PKD1) Is a New Functional Non-Genomic Target of Bisphenol A in Breast Cancer Cells. Frontiers in Pharmacology, 2020, 10, pp.1683. ⟨10.3389/fphar.2019.01683⟩. ⟨inserm-03033637⟩
80 View
86 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More