Estrogen receptor-α, progesterone receptor and c-erbB/HER-family receptor mRNA detection and phenotype analysis in spontaneous canine models of breast cancer
Farruk M. Lutful Kabir1,†, Patricia DeInnocentes1, Payal Agarwal2, Christopher P. Mill3,‡, David J. Riese II3, R. Curtis Bird1,*
AURIC - Auburn University Research Initiative in Cancer
1Department of Pathobiology, College of Veterinary Medicine, Harrison School of Pharmacy, Auburn University, AL 36849
2Scott-Ritchey Research Center, College of Veterinary Medicine, Harrison School of Pharmacy, Auburn University, AL 36849
3Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, AL 36849
Correspondence to: Tel: +1-334-844-2707; Fax: +1-334-844-2652; E-mail: birdric@auburn.edu
Present address: Department of Pediatrics, Division of Pulmonology, University of Alabama, Birmingham, AL 35294 USA
Present address: St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105 USA
Received: February 11, 2016; Revised: June 2, 2016; Accepted: July 21, 2016; Published online: August 10, 2016.
Abstract
Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3 and c-erbB-4 receptors. This investigation developed and validated QrtPCR assays for each transcript to provide rapid assessment of breast cancer phenotype for canine cancers, based on ER1, PR and c-erbB-2/HER2 expression, similar to human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expression in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of canine mammary tumor-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.
Keywords: canine, breast cancer, mammary epithelial cells, estrogen/progesterone receptor, c-erbB/HER-2 receptor


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