R. Das et al., Expression pattern of fatty acid-binding proteins in human normal and cancer prostate cells and tissues, CLIN CANC R, 7(6), 2001, pp. 1706-1715
Purpose: Fatty acid-binding protein (FABP) expression patterns were evaluat
ed as potential markers and therapeutic targets for prostate cancer.
Experimental design: FABP expression levels were determined by reverse tran
scription-PCR in cultured prostate normal and tumor cells and in human biop
sy samples, Regulation of cellular processes,vas examined using FABP antise
nse constructs.
Results: Prostate cells express a variety of different FABPs. Liver (L)- an
d intestine-FABPs were elevated 5-9-fold in prostate cancer compared with n
ormal primary prostate cells, In contrast, adipose- and epidermal-FABPs wer
e markedly down-regulated (3-20-fold) in cancer versus normal cells, Simila
r expression patterns mere found in human tissue biopsy samples. However, b
rain-FABP had a distinct pattern of expression: it was overexpressed only i
n 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 prost
ate epithelial cells. Antisense oligodeoxynucleotides, designed to block pr
oduction of epidermal-FABP (a marker for normal prostate cells), caused inc
reased proliferation in DU 145 prostate cancer cells. In vivid contrast, an
tisense oligodeoxynucleotides to L-FABP (overexpressed in prostate cancer)
decreased proliferation and caused apoptosis,
Conclusions: We propose that there is a distinct balance between these grou
ps 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 o
f prostate cancer.