miRNA-214-3p stimulates carcinogen-induced mammary epithelial cell apoptosis in mammary cancer-resistant species

Abstract

Mammary cancer incidence varies greatly across species and underlying mechanisms remain elusive. We previously showed that mammosphere-derived epithelial cells from species with low mammary cancer incidence, such as horses, respond to carcinogen 7, 12-Dimethylbenz(a)anthracene-induced DNA damage by undergoing apoptosis, a postulated anti-cancer mechanism. Additionally, we found that miR-214-3p expression in mammosphere-derived epithelial cells is lower in mammary cancer-resistant as compared to mammary cancer-susceptible species. Here we show that increasing miR-214 expression and decreasing expression of its target gene nuclear factor kappa B subunit 1 in mammosphere-derived epithelial cells from horses abolishes 7,12-Dimethylbenz(a)anthracene-induced apoptosis. A direct interaction of miR-214-3p with another target gene, unc-5 netrin receptor A, is also demonstrated. We propose that relatively low levels of miR-214 in mammosphere-derived epithelial cells from mammals with low mammary cancer incidence, allow for constitutive gene nuclear factor kappa B subunit 1 expression and apoptosis in response to 7, 12-Dimethylbenz(a)anthracene. Better understanding of the mechanisms regulating cellular responses to carcinogens improves our overall understanding of mammary cancer resistance mechanisms.

The mammosphere-derived epithelial cell secretome modulates neutrophil functions in the bovine model

“…Images of blots were captured on a ChemiDoc Touch Imaging System and band intensities of proteins of interest relative to reference protein bands were determined using Image Lab software (both from Bio Rad). We and other groups have previously used ubiquitously expressed secreted and structural proteins as references for equal loading across CM samples in WB ( 57 , 60 , 61 ). To determine a suitable reference protein for the bovine MDEC CM samples in this study, CM from 3 bovine MDEC lines were run on a WB, each as undiluted, diluted 1:2, and diluted 1:4.…”

Using Organoids to Tap Mammary Gland Diversity for Novel Insight

“…Several hypotheses can explain the rarity of mammary tumors in some species. It has been hypothesized that differences in DNA damage response between mammary cancer-resistant and susceptible species, and particularly in the threshold of DNA damage that leads to apoptosis, could explain the survival vs. elimination of damaged cells in susceptible vs. resistance species, respectively [ 74 – 76 ]. Limited data supporting this hypothesis was collected in 2D models of mammary epithelial cells derived from relevant species but was not verified in 3D or in-vivo.…”