Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats.
Artikel i vetenskaplig tidskrift, 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

Författare

Emma Samuelson

Göteborgs universitet

Carola Hedberg

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Afrouz Behboudi

Göteborgs universitet

Endocrine-Related Cancer

1351-0088 (ISSN)

Vol. 16 1 99-111

Ämneskategorier

Cell- och molekylärbiologi

Medicinsk genetik

DOI

10.1677/ERC-08-0185

PubMed

19075038