Novel Human Prostate Epithelial Cell Cultures.

Abstract

Prostate cancer is the most common male cancer in the USA and the second leading cause of male cancer death in the USA. African American men have higher incidence and mortality rate from prostate cancer compared to Caucasian men in North America, indicating the prostate cancer is a major public health problem in this population. Studies of prostate cancer have been hampered by various factors including (1) restricted access to tissues, (2) difficulties in propagating premalignant lesions and primary prostate tumors in vitro, and (3) limited availability of prostate cell lines for in vitro studies. There is no commercially available pair of non-malignant and tumor cells derived from the same prostate cancer patient. Primary prostate 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. To examine these early stages, we have developed in vitro models of prostate epithelial cell immortalization. Generation of human primary epithelial (HPE) cells has been achieved using the serum-free keratinocyte growth medium. Retrovirus containing human telomerase reverse transcriptase (hTERT) was also used for the generation of primary non-malignant and malignant tumor cells. In addition, we have established the first immortalized cell lines of a pair of non-malignant and malignant tumors derived from an African American prostate cancer patient. Interestingly, we have found that the Rock inhibitor and feeder cells induced the conditioned reprogramming (CR) of epithelial cells-normal and tumor epithelial cells from many tissues to proliferate indefinitely in vitro, without transduction of viral or cellular genes. More recently, using CR, we have established normal and tumor cultures respectively from a patient prostatectomy. These CR cells grow indefinitely in vitro and retain stable karyology. The tumor-derived CR cells produced tumors in SCID mice. The use of novel pair of non-malignant and malignant tumor cells derived from the same patient provides a unique in vitro model for studies of early prostate cancer and for testing preventive and therapeutic regimens.