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Expression Pattern of Fatty Acid-binding Proteins in Human Normal and Cancer Prostate Cells and Tissues¹

Walter Reed Army Institute of Research, Division of Pathology, Washington, DC 20307 [R. D., R. H., R. N., M. J.]; Veterans Administration Healthcare System, Pittsburgh, Pennsylvania 15240 [M. M.]; and The University of Pittsburgh, Pittsburgh, Pennsylvania 15240 [M. M.]

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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