RGD Reference Report - Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas. - Rat Genome Database

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Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas.

Authors: Dumur, CI  Campbell, DJ  Dewitt, JL  Oyesanya, RA  Sirica, AE 
Citation: Dumur CI, etal., Exp Mol Pathol. 2010 Dec;89(3):227-35. Epub 2010 Sep 9.
RGD ID: 4889598
Pubmed: PMID:20816680   (View Abstract at PubMed)
PMCID: PMC2981699   (View Article at PubMed Central)
DOI: DOI:10.1016/j.yexmp.2010.08.007   (Journal Full-text)

Previously, we described an orthotopic cholangiocarcinoma model based on bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats, which closely mimics clinical features of early versus advanced stages of the human cancer. We now used gene expression microarray together with quantitative real-time RT-PCR to profile genes differentially expressed in highly tumorigenic BDEneu cells and corresponding tumors compared to less aggressive tumorigenic BDEsp cells and tumors. Genes identified as being commonly overexpressed in parent BDEneu cells, tumors, and in a BDEneu tumor-derived cholangiocarcinoma cell line included Sox17, Krt20, Erbb2, and Sphk1 when respectively compared to BDEsp cells, tumors, and tumor-derived BDEsp cholangiocarcinoma cells. Muc1 was also prominently overexpressed in BDEneu cells and tumor-derived cholangiocarcinoma cells over that expressed in corresponding BDEsp cell lines. Periostin and tenascin-C, which were produced exclusively by cholangiocarcinoma-associated fibroblastic cells, were each significantly overexpressed in BDEneu tumors compared to BDEsp tumors. Interestingly, amphiregulin was representative of a gene found to be significantly underexpressed in vitro in BDEneu cells compared to BDEsp cells, but significantly overexpressed in BDEneu tumors compared to BDEsp tumors, and correlated with BDEneu cholangiocarcinoma progression in vivo. Our data support a unique animal model that recapitulates important molecular features of human cholangiocarcinoma progression, and may serve as a potentially powerful preclinical platform for identifying and rapidly testing novel molecular targeting strategies for cholangiocarcinoma therapy and/or prevention.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cholangiocarcinoma severityISOSox17 (Rattus norvegicus)4889598; 4889598 RGD 
cholangiocarcinoma severityIEP 4889598; 4889598 RGD 
cholangiocarcinoma severityISOTnc (Rattus norvegicus)4889598; 4889598 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sox17  (SRY-box transcription factor 17)
Tnc  (tenascin C)

Genes (Mus musculus)
Sox17  (SRY (sex determining region Y)-box 17)
Tnc  (tenascin C)

Genes (Homo sapiens)
SOX17  (SRY-box transcription factor 17)
TNC  (tenascin C)


Additional Information