Adipocyte-fatty acid binding protein induces apoptosis in DU145 prostate cancer cells.
Adipocyte-fatty acid binding protein (A-FABP) is a 14-15 kDa cytoplasmic protein that binds unesterified fatty acids (FA). It is believed that A-FABP is present in normal cells and disappears in cancer cells. Prostate cancer DU145 cells lack expression of A-FABP. Here, we report that transfection of A-FABP blocked growth of DU145 cells suggesting its role as a tumor suppressor. A-FABP transfected- prostate cancer DU145 cells underwent apoptosis when induced to overexpress A-FABP using an ecdysone-controlled expression system. DU145 cell cultures in complete medium exhibited a maximum of approximately 28% of apoptotic cells after 96 h of exposure to an ecdysone analog, Ponasterone A. We found that the possible mechanisms leading to the observed apoptotic effect may be due, in part, to an overexpression of tumor necrosis factor-alpha (TNF-alpha) and a moderate downregulation of transforming growth factor-alpha (TGF-alpha) in DU145 cells overexpressing A-FABP. The epidermal growth factor receptor (EGFR)/phosphatidyl inositol 3-kinase (PI 3-kinase) signaling pathway was not altered in these cells, suggesting that A-FABP may cause apoptosis by inducing downregulation of essential autocrine growth factors and/or upregulation of pro-apoptotic ones.
De Santis
Marta L
ML
Department of Molecular Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
Hammamieh
Rasha
R
Das
Rina
R
Jett
Marti
M
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004441:Ecdysterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000494:pharmacology; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D013256:Steroids; D016211:Transforming Growth Factor alpha; D014409:Tumor Necrosis Factor-alpha; D004441:Ecdysterone; C008999:ponasterone A