Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro prostate cell models.

Abstract

Prostate cancer is the most commonly diagnosed malignancy in the United States, as well as in the Western world, and the second leading cause of male cancer death in the United States. Despite its high incidence, the molecular and genetic events involved in prostate cancer progression remain poorly understood. A hurdle in understanding the molecular genetic changes in prostate cancer has been the difficulty in establishing premalignant lesions and primary prostate tumors as in vitro cell cultures. Primary epithelial cells grow for a finite life span and then senesce. Immortalization is defined by continuous growth of otherwise senescing cells and is believed to represent an early stage in tumor progression. In order to examine these early stages, we and others have developed in vitro models of prostate epithelial cell immortalization. Because prostate cancer is a multistep, progressive disease with a typical onset later in life and with an usually high number of latent cases that do not develop into clinically manifest cancer, the steps in the progression to malignancy are of particular interest. To understand the many factors that are suspected to contribute to the development of this malignancy, there is a need for an in vitro multistep human prostate epithelial culture system. These models have been extremely important in identifying genetic and molecular changes involved in prostate cancer progression. Recently, novel human cell culture models for the study of prostate cancer have been developed. Successful establishment of primary prostate cancer cell lines from patients' familial and sporadic prostate cancer has been accomplished using telomerase, the gene that prevents cellular senescence. The novel models will be useful for identification and characterization of prostate cancer genes and will provide the new means for testing for chemoprevention and chemotherapeutic agents.