Norman Greenberg, Ph.D.
Jeff Rosen, Ph.D.
Robert Matusik, Ph.D.*

Departments:

Cell Biology (Baylor) and Physiology* (Univ. of Manitoba)

Description:

The investigators have established a transgenic mouse model for prostate cancer using the probasin transgene targeting system. This system consists of 426 basepairs of the rat probasin gene promoter and 28 basepairs of 5'-untranslated region plus a specific oncogene in order to induce oncogenesis in the mouse prostate. The resulting strains of mice exhibit consistent prostate-specific patterns of expression and progressively develop prostatic intraepithelial neoplasia (PIN), focal adenocarcinoma and finally, metastatic spread to the lymph nodes, adrenal glands, lung and bone.

Applications/Advantages:

Prostate cancer is the cause of death in approximately 41,000 American men each year. In addition, more than 180,000 new cases of prostate cancer are discovered annually. Based on these figures, a tremendous market opportunity exists for new pharmaceutical treatments as well as gene therapy applications. Unfortunately, rapid progress in prostate cancer research has been slowed, in part, by the lack of an adequate animal model to mimic the progression of human prostate cancer.

This transgenic mouse model will be an essential research tool for academic and commercial companies by enabling the rapid screening of novel compounds and testing of new gene-based therapies for treatment of prostate cancer. The mice developed by the inventors have several distinct advantages over existing models:

• the transgene is specific for the epithelial cells of the prostate
• the tumor tissue histologically and biochemically resembles the human disease (with PIN and cribriform structures appearing as early as 10 weeks)
• the tumors arise with a short latency period and with 100% frequency
• the mice exhibit progressive stages of prostate cancer ranging from PIN, cribriform structures, and focal adenocarcinoma to extracapular extension (ECE), seminal vesicle invasion (SVI) with metastasis to lymph nodes, adrenal glands, lung and bone
• the mouse model can be used to follow the progression/multi-stage development of disease all within a 10 - 20 week time period
• the mouse models exhibit less morbidity and mortality due to complications with other organs as seen in other models

Technology Status:

Transgenic mice that express a particular oncogene and subsequently develop local and metastatic forms of prostate cancer have been developed. Currently, one established line is available in either an inbred C57Bl/6 genetic background or as C57/FVB hybrids. A paper describing the transgenic mouse model for prostate cancer has appeared in PNAS.

Patent Status:

U.S. Patent 5,907,078 Awarded May 25, 1999

Availability:

Available for non-exclusive or exclusive license.

OTA: 94-45 Reviewed 9/26/95