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E Samuelson, Cell and Molecular Biology-Genetics, University of Gothenburg, Gothenburg, Sweden
C Hedberg, Cell and Molecular Biology-Genetics, University of Gothenburg, Gothenburg, Sweden
S Nilsson, Mathematical Statistics, Chalmers University of Technology, Gothenburg, Sweden
A Behboudi, Institute of Biomedicine, Department of Clinical Genetics, University of Gothenburg, Gothenburg, Sweden

Correspondence: Afrouz Behboudi, Email: afrouz.behboudi{at}gu.se

Abstract

Female rats of the BDII inbred strain are prone to spontaneously develop endometrial carcinomas that in cell biology and pathogenesis are very similar to those of human. Human endometrial carcinomas are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS and CTNNB1 (β-CATENIN) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (CADHERIN 1 or E-CADHERIN) expression. However, many human endometrial carcinomas have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The endometrial carcinomas developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1 and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of endometrial carcinomas in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Ifr1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous endometrial carcinomas in BDII rats can be related to high-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.