Abstract

Abstract : The first aim is to identify prostatic stem cells using an intraprostatic transplantation approach using GFP-tagged prostatic basal and luminal cell lines that we established. We found that both basal and luminal cells engraft and that engrafted basal cells give rise to luminal cells. The second aim studies the characteristics of prostatic tumors that arise after ras transformation of basal and luminal cells. We show that the transformed basal and luminal cell lines form subcutaneous tumors and that the rate of tumor growth is enhanced by co-inoculation with normal prostatic smooth muscle cells. This indicates that smooth muscle cells may contribute to the progression of prostatic tumors and that paracrine signaling between basal and smooth muscle cells may be involved in tumorigenesis. We also show that intraprostatic inoculation of transformed basal cells gives rise to tumors that contain luminal cells. This is significant as it may explain why most prostatic tumors have a luminal phenotype. Prostatic stem cells are considered to be of basal origin and stem cells are the likely targets of transformation leading to prostate cancer. Our results may explain this paradox as transformed basal cells may give rise to transformed luminal cells that may have a growth advantage. Hence by the time the cancer is clinically manifest most of the cells in the tumor may be luminal in nature.

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