Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats.
Journal article, 2009
Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC 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 (beta-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 EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC 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 EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 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 EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.
genetics
Cadherins
beta Catenin
Inbred Strains
Glycoproteins
genetics
Adenocarcinoma
genetics
Male
Rats
Cyclin-Dependent Kinase Inhibitor p16
Tumor Suppressor Protein p53
Alleles
Reverse Transcriptase Polymerase Chain Reaction
genetics
Rats
Female
Neoplastic
PTEN Phosphohydrolase
Endometrial Neoplasms
genetics
Interferon Regulatory Factor-1
classification
genetics
Mutation
Animals
physiology
Gene Expression Regulation
classification
genetics
genetics
genetics
Endometrium
Author
Emma Samuelson
University of Gothenburg
Carola Hedberg
University of Gothenburg
Staffan Nilsson
University of Gothenburg
Chalmers, Mathematical Sciences, Mathematical Statistics
Afrouz Behboudi
University of Gothenburg
Endocrine-Related Cancer
1351-0088 (ISSN) 14796821 (eISSN)
Vol. 16 1 99-111Subject Categories
Cell and Molecular Biology
Medical Genetics
DOI
10.1677/ERC-08-0185
PubMed
19075038