RGD Reference Report - Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats. - Rat Genome Database

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Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats.

Authors: Samuelson, E  Hedberg, C  Nilsson, S  Behboudi, A 
Citation: Samuelson E, etal., Endocr Relat Cancer. 2009 Mar;16(1):99-111. Epub 2008 Dec 15.
RGD ID: 5128782
Pubmed: PMID:19075038   (View Abstract at PubMed)
DOI: DOI:10.1677/ERC-08-0185   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IRF1Humanendometrial adenocarcinoma  ISOIrf1 (Rattus norvegicus)DNA:deletions (rat)RGD 
Irf1Ratendometrial adenocarcinoma  IAGP DNA:deletions (rat)RGD 
Irf1Mouseendometrial adenocarcinoma  ISOIrf1 (Rattus norvegicus)DNA:deletions (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Irf1  (interferon regulatory factor 1)

Genes (Mus musculus)
Irf1  (interferon regulatory factor 1)

Genes (Homo sapiens)
IRF1  (interferon regulatory factor 1)


Additional Information