A Claude-Taupin

A Rangarajan

B Etschmann

C Mund

C Penzo

CH O'Neill

CR Keese

David J. Argyle

DM Vail

E Kaminskas

F Chik

Gerlinde R. Van de Walle

GM Nagaraja

GS Mack

HD Soule

HW Chang

J Hong

JF Modiano

L Liu

L Munson

LC Penning

LG Wolfe

LJ Young

M Kadota

MB Lustberg

N Sato

P Pesavento

P Uva

PJ Keller

R Connolly

R Sandhu

Rebecca M. Harman

RW Else

S Borowicz

S Karsli-Ceppioglu

S Thakur

Scott A. Coonrod

SJ Santner

SS Pinho

T Cluzeau

T Fujikane

T Kiziltepe

TC Wright

Theresa M. Curtis

TS Xia

Y Yuan

Murine models are indispensible for the study of human breast cancer, but they havelimitations: tumors arising spontaneously in humans must be induced in mice, and long-term follow up is limited by the short life span of rodents. In contrast, dogs and cats develop mammary tumors spontaneously and are relatively long-lived. This studyexamines the effects of the DNA methyltransferase (DNMT) inhibitor 5-Azacytidine (5-AzaC) on normal and tumoral mammary cell lines derived from dogs, cats and humans, as proof of concept that small companion animals are useful models of human breast cancer. Our findings show that treatment with 5-AzaC reduces in vitro tumorigenicity in all three species based on growth and invasion assays, mitochondrial activity and susceptibility to apoptosis. Interestingly, we found that the effects of 5-AzaC on gene expression varied not only between the different species but also between different tumoral cell lines within the same species, and confirmed the correlation between loss of methylation in a specific gene promotor region and increased expression of the associated gene using bisulfite sequencing. In addition, treatment with a high dose of 5-AzaC was toxic to tumoral, but not healthy, mammary cell lines from all species, indicating this drug has therapeutic potential. Importantly, we confirmed these results in primary malignant cells isolated from canine and feline adenocarcinomas. The similarities observed between the three species suggest dogs and cats can be useful models for the study of human breast cancer and the pre-clinical evaluation of novel therapeutics

Harman, Rebecca M.

Curtis, Theresa M.

Argyle, David

Coonrod, Scott A.

Van de Walle, Gerlinde R.

Edinburgh Research Explorer

A comparative study on the in vitro effects of the DNA methyltransferase inhibitor 5-Azacytidine (5-AzaC) in breast/mammary cancer of different mammalian species

Crossref

Journal of Mammary Gland Biology and Neoplasia

A Comparative Study on the In Vitro Effects of the DNA Methyltransferase Inhibitor 5-Azacytidine (5-AzaC) in Breast/Mammary Cancer of Different Mammalian Species

https://www.pure.ed.ac.uk/ws/files/24554526/Microsoft_Word_Revised_manuscript_J_MGB_N_without_Tables.docx_copy.pdf

A comparative study on the in vitro effects of the DNA methyltransferase inhibitor 5-Azacytidine (5-AzaC) in breast/mammary cancer of different mammalian species

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