Oncotarget

Research Papers:

Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene (DMBA)-treated mammary stem/progenitor cells from species with varying mammary cancer incidence

Melissa M. Ledet, Meghan Oswald, Robyn Anderson and Gerlinde R. Van de Walle _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:32761-32774. https://doi.org/10.18632/oncotarget.25988

Metrics: PDF 342 views  |   HTML 1117 views  |   ?  


Abstract

Melissa M. Ledet1, Meghan Oswald1, Robyn Anderson1 and Gerlinde R. Van de Walle1

1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca 14853, NY, USA

Correspondence to:

Gerlinde R. Van de Walle, email: grv23@cornell.edu

Keywords: mammary stem/progenitor cells; DMBA; mammary cancer; DNA damage; apoptosis

Received: May 16, 2018     Accepted: July 31, 2018     Published: August 28, 2018

ABSTRACT

A natural variation exists in the susceptibility to mammary cancer among wild and domestic mammalian species. Mammary stem/progenitor cells (MaSC) represent a primary target cell for transformation; however, little is known about the intrinsic response of these cells to carcinogenic insults. Polycyclic aromatic hydrocarbons (PAH), such as 7,12-dimethylbenz[a]anthracene (DMBA), are abundantly present in the environment and have been linked to the development of mammary cancer in humans and rodents. We treated MaSC from equine (mammary cancer-resistant) and canine (mammary cancer-susceptible) species with DMBA and assessed cytochrome P450 metabolic activity, DNA damage and viability. Our notable findings were that MaSC from both species showed DNA damage following DMBA treatment; however, equine MaSC initiated cell death whereas canine MaSC repaired this DNA damage. Follow-up studies, based on genome-wide transcriptome analyses, revealed that DMBA induced activation of both the intrinsic and extrinsic apoptotic pathways in equine, but not canine, MaSC. Based on these findings, we propose a hypothetical model in which undergoing apoptosis in response to an oncogenic event might contribute to a lower incidence of mammary cancer in certain mammalian species. Such a mechanism would allow for the elimination of DNA-damaged MaSC, and hence, reduce the risk of potential tumor-initiating mutations in these cells.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 25988