RGD Reference Report - Independent amplification of two gene clusters on chromosome 4 in rat endometrial cancer: identification and molecular characterization. - Rat Genome Database

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Independent amplification of two gene clusters on chromosome 4 in rat endometrial cancer: identification and molecular characterization.

Authors: Walentinsson, A  Helou, K  Wallenius, V  Hedrich, HJ  Szpirer, C  Levan, G 
Citation: Walentinsson A, etal., Cancer Res 2001 Nov 15;61(22):8263-73.
RGD ID: 70557
Pubmed: PMID:11719459   (View Abstract at PubMed)

The BDII rat is genetically predisposed to hormone-dependent endometrial adenocarcinoma and was used to model human cancer. Tumors arising spontaneously in strain crosses involving BDII rats were analyzed by means of comparative genome hybridization. The most common aberration was amplification of the proximal region of rat chromosome 4, centered around bands q12-q22. The copy numbers of 15 cancer-related genes from the region were examined in tissue cultures of 11 endometrial carcinomas (10 endometrial adenocarcinomas and 1 endometrial squamous cell carcinoma) and one peritoneal mesothelioma. Amplification in rat chromosome 4 was detected in six tumors (50%), five of which carried two separate amplified regions, situated at 4q12-q13 and 4q21-q22, interrupted by a nonamplified segment at 4q13-q21.1. The genes Cdk6 (cyclin-dependent kinase 6) and Met (hepatocyte growth factor receptor) were located in the core of each amplified region and were amplified most recurrently and at the highest levels among the genes tested. Using fluorescence in situ hybridization on tumor metaphases, it was observed that the amplified Cdk6 and Met sequences were situated on typical homogeneously staining regions (HSRs). In three tumors, both genes were amplified in the same HSRs, whereas in two tumors, the amplified sequences of each gene were situated in separate HSRs. In addition, Cdk6 and Met amplification was consistently associated with a corresponding increase in gene expression, suggesting that the two genes might represent the targets for the amplifications. In the sixth tumor, which carried amplified sequences of Met but not of Cdk6, coexpression of Met and the normally silent hepatocyte growth factor gene (Hgf; the ligand of Met) was observed. This finding suggests that an autocrine signaling circuit might be operating in this particular tumor. Taken together, our findings suggest that up-regulation of Cdk6 and/or Met may contribute to the development of endometrial cancers in the BDII rat.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Endometrial Neoplasms  ISOMet (Rattus norvegicus)70557; 70557DNA:amplificationRGD 
Endometrial Neoplasms  IAGP 70557DNA:amplificationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Met  (MET proto-oncogene, receptor tyrosine kinase)

Genes (Mus musculus)
Met  (met proto-oncogene)

Genes (Homo sapiens)
MET  (MET proto-oncogene, receptor tyrosine kinase)

Objects referenced in this article
Gene Abcb1b ATP-binding cassette, sub-family B member 1B Rattus norvegicus
Gene Arhgef5 Rho guanine nucleotide exchange factor 5 Rattus norvegicus
Gene Asns asparagine synthetase (glutamine-hydrolyzing) Rattus norvegicus
Strain BDII/Ztm null Rattus norvegicus
Gene Braf B-Raf proto-oncogene, serine/threonine kinase Rattus norvegicus
Gene Cav1 caveolin 1 Rattus norvegicus
Gene Cdk5 cyclin-dependent kinase 5 Rattus norvegicus
Gene Cdk6 cyclin-dependent kinase 6 Rattus norvegicus
Gene Cftr CF transmembrane conductance regulator Rattus norvegicus
Gene Cyp51 cytochrome P450, family 51 Rattus norvegicus
Gene Dmtf1 cyclin D binding myb-like transcription factor 1 Rattus norvegicus
Gene Hgf hepatocyte growth factor Rattus norvegicus
Gene Smo smoothened, frizzled class receptor Rattus norvegicus
Gene Tac1 tachykinin, precursor 1 Rattus norvegicus
Gene Wnt2 Wnt family member 2 Rattus norvegicus

Additional Information