FAS expression inversely correlates with PTEN level in prostate cancer and a PI 3-kinase inhibitor synergizes with FAS siRNA to induce apoptosis.
Fatty acid synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer and is, therefore, considered to be an attractive target for anticancer therapy. However, the exact mechanism of overexpression of the FAS gene in tumor cells is not well understood. In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro. We also found that the combination of the expression status of these two genes is a better prognostic marker than either gene alone. Furthermore, our results indicate that the specific inhibition of FAS gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.
Bandyopadhyay
Sucharita
S
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL 62702, USA.
Pai
Sudha K
SK
Watabe
Misako
M
Gross
Steven C
SC
Hirota
Shigeru
S
Hosobe
Sadahiro
S
Tsukada
Taisei
T
Miura
Kunio
K
Saito
Ken
K
Markwell
Stephen J
SJ
Wang
Ying
Y
Huggenvik
Jodi
J
Pauza
Mary E
ME
Iiizumi
Megumi
M
Watabe
Kounosuke
K
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
D025521:Tumor Suppressor Proteins; D064429:Fatty Acid Synthases; D019869:Phosphatidylinositol 3-Kinases; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human