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Apoptosis and Tumor Progression in Prostate Cancer

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Final rept. 1 Feb 2001-31 Jan 2006

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In the period covered by this application we have standardized an efficient methodologies for isolating cells from primary tumors expressing RFP by fluorescence activated cell sorting FACS and by laser capture micro-dissection LCM. We have completed a comprehensive micro-array based bioinformatics effort to identify genes whose expression is modulated by Casodex to characterize the molecular events underlying the effects of Casodex on AR cell lines LNCaP and PC-346C cells The changes in gene expression detected by micro-array were validated by QT-PCR using SYBR green. The results of these experiments are also being compared to the changes in gene expression seen in the PC-346RFP primary tumors and metastases from animals chronically treated with Casodex. We have also demonstrated that there is a threshold dose response to Casodex in these cell lines. Results of the dose response revealed considerable differences in expression changes of target genes between Casodex treatments of 50 or 100 M in comparison to control. One of these genes, the cell cycle inhibitor p21 which has been recently shown to have multiple transcript variants also demonstrates differential regulation of the transcripts at the two concentrations. One of the variants, p21B, has been implicated in apoptosis and displays upregulation at concentrations of Casodex that induce cell death. Ingenuity pathway analysis suggest that this gene may be dually regulated by p53 and AR at the higher dose of Casodex.

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  • Biochemistry
  • Medicine and Medical Research

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