Differential signaling pathway activation in 7,12-dimethylbenz[a] anthracene (DMBA)-treated mammary stem/progenitor cells from species with varying mammary cancer incidence
| Autor: | Gerlinde R. Van de Walle, Melissa M. Ledet, Meghan Oswald, Robyn Anderson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Programmed cell death DMBA DNA damage 7 12-Dimethylbenz[a]anthracene apoptosis Biology Transcriptome 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Oncology chemistry mammary cancer Apoptosis 030220 oncology & carcinogenesis Cancer research Progenitor cell Carcinogen mammary stem/progenitor cells Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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