Molecular impacts of antisense complementary to the liver fatty acid binding protein (FABP) mRNA in DU 145 prostate cancer cells in vitro.
Previous studies in our laboratory have showed that liver (L)-FABP and intestine-FABP were upregulated in prostate cancer cells whereas Adipose-FABP and epidermal-FABP were down regulated in cancer cells when compared to normal cells in tissue cultures and biopsy samples (Das et al, 2001). We have also shown that blocking the expression of L-FABP resulted in remarkable effects on apoptosis and cell proliferation of prostate cancer cell lines. Another study showed that induction of A-FABP inhibited proliferation DU 145 prostate cancer cells (DeSantis et. al., Journal of Experimental Therapeutics and Oncology, 4:91-100, 2004) and caused a downregulation of the L-FABP transcript levels. This suggests that there is a correlation in the expression between of A-FABP and L-FABP in prostate cancer cells and that high expression of A-FABP is associated with a downregulation of L-FABP and vice versa. This study examines the mechanism by which L-FABP antisense regulates proliferation and apoptosis in prostate cancer cell lines. We used human cDNA array blots and custom DNA microarrays to explore differentially expressed genes in DU 145 prostate cancer cells treated with L-FABP antisense oligonucleotide. Genes that were differentially expressed were confirmed using quantitative RT-PCR. Genes correlating with proliferation were downregulated and antiproliferative genes were upregulated in response to antisense to L-FABP. This suggests a possible use of these antisense ODNs as therapeutic agents for prostate cancer in future.
Hammamieh
Rasha
R
Walter Reed Army Institute of Research, Division of Pathology, Silver Spring, MD 20910, USA. Rasha.Hammamieh@NA.AMEDD.ARMY.MIL
Chakraborty
Nabarun
N
Das
Rina
R
Jett
Marti
M
D000943:Antigens, Differentiation; D017209:Apoptosis; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics* / Q000494:pharmacology; D049109:Cell Proliferation; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D002352:Carrier Proteins; C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger