Rodent models for targeted oncogenesis of the prostate gland.

Currently, prostate cancer ranks as the most frequent non-skin malignancy detected in males. Yet, of the major human cancers, it remains one of the least understood in terms of its molecular and genetic basis. Research on prostate cancer has been limited by the paucity of tissues available for study. Much of the tissue obtained through surgery for localized prostate cancer will be required for pathological staging and grading. The more aggressive forms of prostate cancer are usually detected subsequent to metastatic involvement at which point there is little reason to surgically remove the prostate tumor(s). A final complication is the propensity of prostate cancer to metastasize to the bone, a site extremely difficult to obtain suitable biopsies for study. Further hindering research efforts on prostate cancer is the lack of suitable animal models for study. In contrast to its frequent occurrence in humans, prostate cancer is a rare event in most other mammalian species, particularly laboratory rodents. Therefore, in order to make this disease more amenable for study, there is a growing effort to identify or develop a means to target oncogenesis to the prostate gland of rodents. As will be reviewed here, this goal is being approached with the use of 3 different methods; one that takes advantage of the unique androgenic hormone requirement for prostate growth to exaggerate the effects of carcinogens at that site and two methods (recombinant retrovirus transduction prior to organ reconstitution and transgenic targeting) that allow direct genetic manipulation of cells in the prostate gland leading to the development of prostatic malignancy.