Gastrointestinal stromal tumours overexpress fatty acid synthase.
Fatty acid synthase (FASN), a key enzyme for de novo lipogenesis, is overexpressed in many malignant tumours and is associated with aggressive biological behaviour. FASN expression and its possible relationship with more aggressive behaviour in gastrointestinal stromal tumours (GISTs) have not been addressed to date. Here, FASN expression was assessed by immunohistochemistry in 60 primary GISTs (28 low/intermediate risk and 32 high risk) and seven metastatic GISTs. Sixteen smooth muscle gastrointestinal tumours were used as controls. FASN was overexpressed in 36 of 60 GISTs (60%): in 12 of 28 (42%) low/intermediate-risk GISTs and in 24 of 32 (75%) high-risk GISTs (p<0.05). Two primary and seven metastatic GISTs and five GIST cell lines (GIST882, GIST430, GIST522, GIST62, and GIST48), analysed by western blot, showed variable FASN expression. Most metastatic samples expressed high levels of FASN protein. Additionally, seven of 60 GISTs showed a proliferation rate higher than 10% by Ki67 and all of them expressed FASN (p<0.04). Finally, proliferation and apoptosis were investigated after FASN silencing in GIST882 cells, which displayed the highest FASN expression. siRNA-mediated FASN knock-down inhibited expression of the proliferation marker cyclin A, whereas no changes in p27 and cleaved PARP expression were seen. It is concluded that FASN is preferentially overexpressed in high-risk and metastatic GISTs, and that its overexpression likely contributes to cell proliferation.
Department of Pathology, Regional Hospital, Treviso, Italy, and Department of Medical Oncology, Harvard Medical School, Boston, MA, USA.
S
S
Rossi
W
W
Ou
D
D
Tang
N
N
Bhattacharya
A P
AP
Dei Tos
J A
JA
Fletcher
M
M
Loda
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D049109:Cell Proliferation; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D020868:Gene Silencing; D006801:Humans; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D064429:Fatty Acid Synthases