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Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues.
PURPOSE: Fatty acid-binding protein (FABP) expression patterns were evaluated as potential markers and therapeutic targets for prostate cancer.
EXPERIMENTAL DESIGN: FABP expression levels were determined by reverse transcription-PCR in cultured prostate normal and tumor cells and in human biopsy samples. Regulation of cellular processes was examined using FABP antisense constructs.
RESULTS: Prostate cells express a variety of different FABPs. Liver (L)- and intestine-FABPs were elevated 5-9-fold in prostate cancer compared with normal primary prostate cells. In contrast, adipose- and epidermal-FABPs were markedly down-regulated (3-20-fold) in cancer versus normal cells. Similar expression patterns were found in human tissue biopsy samples. However, brain-FABP had a distinct pattern of expression: it was overexpressed only in LNCaP cells and in well-differentiated tissue samples, suggesting a stage-specific expression profile. Secretion of L-FABP protein was observed from DU 145 prostate cancer cells, but not in the culture fluid of normal prostate epithelial cells. Antisense oligodeoxynucleotides, designed to block production of epidermal-FABP (a marker for normal prostate cells), caused increased proliferation in DU 145 prostate cancer cells. In vivid contrast, antisense oligodeoxynucleotides to L-FABP (overexpressed in prostate cancer) decreased proliferation and caused apoptosis.
CONCLUSIONS: We propose that there is a distinct balance between these groups of FABPs, whose altered regulation in cells may play a role in prostate cancer. Furthermore, the pattern of expression and secretion of FABPs have the potential to serve as a diagnostic marker for an aggressive phenotype of prostate cancer.
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