Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues.
OBJECTIVE
Fatty acid-binding protein (FABP) expression patterns were evaluated as potential markers and therapeutic targets for prostate cancer.


METHODS
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.
Das
R
R
Walter Reed Army Institute of Research, Division of Pathology, Washington, DC 20307, USA.
Hammamieh
R
R
Neill
R
R
Melhem
M
M
Jett
M
M
D017209:Apoptosis; D001706:Biopsy; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D002455:Cell Division; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D002352:Carrier Proteins; C493319:FABP1 protein, human; C107608:FABP7 protein, human; C493320:Fabp1 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins