Owen Witte and colleagues have now developed a 'human in mouse' model of prostate cancer that turns the luminal origin theory on its head.
Two main epithelial cell populations are found in human prostate tissue: basal cells, which can be identified by high levels of keratin 5 (K5) and K14 expression, and luminal cells, which are characterized by high levels of K18 and K8 expression. Starting with benign tissue from biopsy samples from patients with prostate cancer, the authors used the basal and luminal keratins as cell markers to sort the two different cell populations. They then transduced both cell populations with a lentivirus that encoded activated AKT and the transcriptional regulator ERG, as well as another lentivirus that encoded the androgen receptor (AR), and these proteins are known to be commonly altered in prostate cancer. The transduced cells were subcutaneously injected into immunodeficient mice. After 16 weeks, only the xenografts from basal cells resulted in the development of adenocarcinoma, which recapitulated the histological and molecular features of the human malignancy. The prostate adenocarcinomas showed an absence of basal cells and an expansion of luminal cells that expressed prostate-specific antigen (PSA), α-methylacyl-coA racemase (AMACR) and AR, all of which are markers of prostatic intraepithelial neoplasia and prostate cancer.
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