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.

Highlights

  • Breast cancer is a leading cause of death in women and is one of the most common cancers in the world today

  • Mouse models of BRCA1 deficiency have been developed in an attempt to understand the role of the gene in vivo (Ma et al, 2010)

  • Porcine Cell Lines and Transfections Primary porcine breast epithelia cells were isolated as described in Prather et al (1999) using a protocol approved by the IACUC of the University of Missouri-Columbia, Columbia, Missouri

Read more

Summary

Introduction

Breast cancer is a leading cause of death in women and is one of the most common cancers in the world today. Women who carry a BRCA1 germ line mutation have a cumulative lifetime risk of 50–85% of developing breast cancer (King et al, 2003). The function of BRCA1 remains poorly understood It has a ubiquitin ligase activity and can control the stability/activity of proteins such as Claspin (Sato et al, 2012) and estrogen receptor alpha (Savage and Harkin, 2015). It is a key player in modulating DNA repair (Zhang and Powell), replication fork stability (Pathania et al, 2011), senescence (Tu et al, 2013), oxidative stress (Marks, 2013), genomic stability (Savage and Harkin, 2015), and checkpoint induced cell

Methods
Results
Conclusion
Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call