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Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats.

Emma Samuelson ; Carola Hedberg ; Staffan Nilsson (Institutionen för matematiska vetenskaper, matematisk statistik) ; Afrouz Behboudi
Endocrine-related cancer (1351-0088). Vol. 16 (2009), 1, p. 99-111.
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: Adenocarcinoma, classification, genetics, Alleles, Animals, Cadherins, genetics, Cyclin-Dependent Kinase Inhibitor p16, genetics, Endometrial Neoplasms, classification, genetics, Endometrium, physiology, Female, Gene Expression Regulation, Neoplastic, Glycoproteins, genetics, Interferon Regulatory Factor-1, genetics, Male, Mutation, PTEN Phosphohydrolase, genetics, Rats, Rats, Inbred Strains, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p53, genetics, beta Catenin, genetics



Denna post skapades 2010-01-14. Senast ändrad 2015-01-16.
CPL Pubid: 107598

 

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Institutioner (Chalmers)

Institutionen för cell- och molekylärbiologi (1994-2011)
Institutionen för biomedicin, avdelningen för medicinsk genetik och klinisk genetik (GU)
Institutionen för matematiska vetenskaper, matematisk statistik (2005-2016)

Ämnesområden

Medicinsk genetik
Molekylärbiologi

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