RGD Reference Report - Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice. - Rat Genome Database

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Progression of prostate cancer from a subset of p63-positive basal epithelial cells in FG/Tag transgenic mice.

Authors: Reiner, T  De Las Pozas, A  Parrondo, R  Perez-Stable, C 
Citation: Reiner T, etal., Mol Cancer Res. 2007 Nov;5(11):1171-9. Epub 2007 Nov 2.
RGD ID: 2315433
Pubmed: PMID:17982114   (View Abstract at PubMed)
DOI: DOI:10.1158/1541-7786.MCR-07-0024   (Journal Full-text)

Transgenic mice that allow targeting of SV40 T antigen (Tag) to the prostate provide a unique model to identify cancer-initiating cells and follow their progression from a normal cell phenotype into prostate cancer cells. We have developed the FG/Tag transgenic mouse model of prostate cancer using the human fetal globin (FG) promoter linked to Tag. Immunohistochemistry results show that before the development of prostate intraepithelial neoplasia (PIN), a subset of p63(+) basal epithelial cells expresses Tag. As in the case of human prostate cancer, there is a loss of p63(+) basal cells with neoplastic progression, and a long period of time is required for PIN lesions to develop into palpable prostate tumors. Other immunohistochemistry results show cellular heterogeneity in FG/Tag PIN lesions and primary tumors with neuroendocrine differentiation. Cell lines derived from primary prostate tumors showed characteristics of a neuroendocrine-epithelial intermediate cell type. The FG promoter has high transcriptional activity in intermediate (DU 145, PC-3) and p63(+) basal epithelial (LHSR-AR) prostate cancer cells. Therefore, the unexpected development of prostate cancer in the FG/Tag mice may be due to the presence of DNA elements in the FG promoter that can target Tag to specific basal or intermediate cells. We conclude that FG/Tag mouse is a unique model of prostate cancer because the initiating cells are a subset of p63(+) basal (possibly stem cells), which may be the true cells of origin for carcinogenesis in aggressive human prostate cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate carcinoma in situ  ISOTrp63 (Mus musculus)2315433; 2315433protein:decreased expression:prostate glandRGD 
prostate carcinoma in situ  IEP 2315433protein:decreased expression:prostate glandRGD 
Prostatic Neoplasms  ISOTrp63 (Mus musculus)2315433; 2315433mRNA:decreased expression:prostate glandRGD 
Prostatic Neoplasms  IEP 2315433mRNA:decreased expression:prostate glandRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tp63  (tumor protein p63)

Genes (Mus musculus)
Trp63  (transformation related protein 63)

Genes (Homo sapiens)
TP63  (tumor protein p63)


Additional Information