title: Positive feedback regulation between Akt phosphorylation and fatty acid synthase expression in osteosarcoma.
abstract: The activation of PI3K/Akt and the overexpression of fatty acid synthase (FASN) are frequently observed in human osteosarcoma (OS). In the present study, in order to investigate the possible association between the phosphorylation of Akt and FASN expression, immunohistochemical staining was conducted on 24 OS specimens from patients with pulmonary metastasis, which revealed a significant positive correlation between phosphorylated Akt (p-Akt) and the expression of FASN (R=0.469, P=0.04). To investigate the association between p-Akt and FASN in vitro, human U2-OS OS cells were treated with FASN-specific RNAi plasmid or LY294002 (an inhibitor of PI3k/Akt). The mRNA levels of Akt and FASN were measured by real-time PCR. Western blot analysis was also performed to detect the protein experession of PI3K, Akt, p-Akt and FASN. The results demonstrated that the PI3K/Akt signaling pathway modulates FASN expression; the inhibition of FASN resulted in the downregulation of p-Akt in the U2-OS cells. Furthermore, the effects induced by the inhibition of the activity of p-Akt or FASN on the malignant phenotype of U2-OS cells were investigated, demonstrating that the malignant phenotype was inhibited by suppressing the activity of PI3K/Akt or FASN in the U2-OS cells. The findings from our study suggest the existence of a positive feedback regulation between Akt phosphorylation and FASN expression and that this loop may play an important role in the malignant phenotype of OS cells.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi, P.R. China.
authors.forename: Qing Feng
authors.initials: QF
authors.lastname: Luo
authors.affiliation: Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, P.R. China.
authors.forename: Ai Fen
authors.initials: AF
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Long
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Tao Fang
authors.initials: TF
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Zhi Li
authors.initials: ZL
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Guo Mei
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Rong Ping
authors.initials: RP
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China.
authors.forename: Wen Zhao
authors.initials: WZ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D054890:Fatty Acid Synthase, Type I / Q000096:biosynthesis / Q000378:metabolism*; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt