Characterization of a New In Vivo Prostate Tumor Model that Progresses to Androgen-Independence and its Application in Determining Changes in Gene Expression
Final rept. 1 Nov 1999-30 Oct 2002
BRITISH COLUMBIA CANCER AGENCY VANCOUVER
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Investigation of the molecular events underlying progression of prostate cancer to androgen-independence has been impeded by the lack of an in vivo model that yields pure populations of prostate cancer cells that are not contaminated with host cells. Here we characterize a new in vivo model that employs hollow fibers and allows for the retrieval of uncontaminated prostate cancer cells during various stages of endocrine progression to androgen-independence. Prostate-specific antigen PSA gene expression, proliferation of cells, and histology were examined before and after castration of the host Approximately 5xlO LNCaP prostate cancer cellsanimal provided measurable levels of PSA in the serum that increased in intact non-castrated animals, decreased 80 to a nadir following castration, and subsequently increased by 4 weeks after castration indicating progression to androgen-independence. In vivo proliferation of LNCaP cells inside fibers continued in the presence of androgens and continued to increase, albeit at a slower rate, in castrated animals Gene expression patterns in this model were consistent with clinical samples and other models when using cDNA arrays to screen RNA isolated from the model Approximately 150 genes were identified to be altered during progression to androgen independence with 77 of these genes having unknown function.
- Medicine and Medical Research