title: A porcine model system of BRCA1 driven breast cancer.
abstract: BRCA1 is a breast and ovarian tumor suppressor. Hereditary mutations in BRCA1 result in a predisposition to breast cancer, and BRCA1 expression is down-regulated in ~30% of sporadic cases. The function of BRCA1 remains poorly understood, but it appears to play an important role in DNA repair and the maintenance of genetic stability. Mouse models of BRCA1 deficiency have been developed in an attempt to understand the role of the gene in vivo. However, the subtle nature of BRCA1 function and the well-known discrepancies between human and murine breast cancer biology and genetics may limit the utility of mouse systems in defining the function of BRCA1 in cancer and validating the development of novel therapeutics for breast cancer. In contrast to mice, pig biological systems, and cancer genetics appear to more closely resemble their human counterparts. To determine if BRCA1 inactivation in pig cells promotes their transformation and may serve as a model for the human disease, we developed an immortalized porcine breast cell line and stably inactivated BRCA1 using miRNA. The cell line developed characteristics of breast cancer stem cells and exhibited a transformed phenotype. These results validate the concept of using pigs as a model to study BRCA1 defects in breast cancer and establish the first porcine breast tumor cell line.
authors.affiliation: Department of Medicine, James Graham Brown Cancer Center, University of Louisville Louisville, KY, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Donninger
authors.affiliation: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville Louisville, KY, USA.
authors.forename: Katharine
authors.initials: K
authors.lastname: Hobbing
authors.affiliation: Department of Biochemistry, University of Louisville Louisville, KY, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Schmidt
authors.affiliation: Division of Animal Sciences, National Swine Resource and Research Center, University of Missouri Columbia, MO, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Walters
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign Urbana, IL, USA.
authors.forename: Laurie
authors.initials: L
authors.lastname: Rund
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign Urbana, IL, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Schook
authors.affiliation: Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, University of Louisville Louisville, KY, USA.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Clark
keywords: BRCA1; SV40 LT; breast cancer; miRNA; transformation