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

Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene (DMBA)-treated mammary stem/progenitor cells from species with varying mammary cancer incidence. Oncotarget. 2018 Aug 28;9(67):32761-32774 Authors: Ledet MM, Oswald M, Anderson R, Van de Walle GR 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 onc...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research