Abstract 5143: Rats heterozygous for Pten develop fibroadenoma and adenocarcinoma arising from the mammary gland

Abstract

Abstract To further characterize the function of the tumor suppressor Pten in the role of tumorigenesis we have created a colony of Pten mutant Sprague Dawley (SD) rats. Utilizing zinc finger nuclease technology we introduced a 7bp deletion in Exon 7 of the Pten gene, creating a frameshift mutation and an early stop codon. Pten homozygous null animals are not viable so a colony of heterozygous animals is maintained. Spontaneous tumors of the mammary gland arise in these animals and were removed for staining and pathological analysis. We describe briefly the creation of this model and preliminary genotypic and proteomic characterization. Further we describe pathological observations made on tumor tissues removed from aging Pten heterozygous animals. We have confirmed a reduction in Pten expression by Western Blot utilizing a monoclonal antibody targeting a central locus in the protein. Heterozygous Pten animals develop spontaneous tumors of the mammary gland which were removed if animals demonstrated deteriorating health or any condition within our Humane Care and Use guidelines. Thirty six tissues from 16 animals were submitted for histopathological analysis. Eight of the animals were male, 8 of the animals were female and had a mean lifespan of 159 days (165 male, 153 female). Remaining consistent with human breast cancer incidence in women below 30 years of age, the most common lesion observed is a benign fibroadenoma (30/36 samples). The malignant adenocarcinoma was observed in 5/36 samples submitted. Fibroadenoma only lesions were observed in 12 of the 16 rats while both fibroadenoma and adenocarcinoma was observed in 4 of the 16 rats. Taken together we believe that a Pten heterozygous rat provides an additional tool for the elucidation of the role of Pten in human cancers. This model may also be useful in the study of neurological disorders such as Autism, Parkinson's disease, Alzheimer's disease, obesity, cardiovascular disease, and diabetes. Mutations in Pten strongly correlate with several human disorders including Cowden syndrome, Bannayan-Zonana syndrome, and Lhermitte-Duclos disease. These disorders result in a tumor pathologies including an increased risk for breast cancers. Citation Format: Aaron M. McCoy, Bala Manickam, Lara Reid, Edward Weinstein, Xiaoxia Cui. Rats heterozygous for Pten develop fibroadenoma and adenocarcinoma arising from the mammary gland. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5143. doi:10.1158/1538-7445.AM2015-5143