Human Prostate Cancer in a Tissue Recombination Model
Abstract
In vivo models based on human epithelial cells (hPrE) provide powerful tools with which to investigate cancer initiation and progression. Tissue recombinations (TR) composed of hPrE and rat urogenital sinus mesenchyme (rUGM) grafted beneath the renal capsule of immunocompromised rodent hosts recapitulate many key events in prostatic development and adult function. The stable integration of known or putative oncogenes into the hPrE component of such TRs is a powerful tool with which to study the effects of these genes in vivo. The cMYC gene (a known oncogene) has been introduced into hPrE. cMYC is expressed in a very tightly regulated manner in non-malignant prostate but is deregulated in PIN and overexpressed/deregulated in high-grade human prostate cancer, suggesting a role in both the pathogenesis of PIN and subsequent progression to cancer. The high efficiency LZRS/Phoenix retroviral system was used to insert the cMYC gene into hPrE under the control of the constitutively active CMV promoter. TR composed of infected hPrE and rUGM were made and grafted into SCID hosts. Hosts were sacrificed after carrying the grafts for 28 days. We have visualized reporter and transgene expression. The TR's showed a rapidly growing metastatic PSA- expressing adenocarcinoma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA421360
Entities
People
- Karin Williams
- Simon W. Hayward
Organizations
- Vanderbilt University Medical Center