Positive feedback regulation between Akt phosphorylation and fatty acid synthase expression in osteosarcoma

Wang,Heng; Luo,Qing Feng; Peng,Ai Fen; Long,Xin Hua; Wang,Tao Fang; Liu,Zhi Li; Zhang,Guo Mei; Zhou,Rong Ping; Gao,Song; Zhou,Yang; Chen,Wen Zhao

doi:10.3892/ijmm.2013.1602

Positive feedback regulation between Akt phosphorylation and fatty acid synthase expression in osteosarcoma

Authors:
- Heng Wang
- Qing Feng Luo
- Ai Fen Peng
- Xin Hua Long
- Tao Fang Wang
- Zhi Li Liu
- Guo Mei Zhang
- Rong Ping Zhou
- Song Gao
- Yang Zhou
- Wen Zhao Chen
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Affiliations: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China, Department of Pathology, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi, P.R. China, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, P.R. China, Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R. China
Published online on: December 23, 2013 https://doi.org/10.3892/ijmm.2013.1602
Pages: 633-639

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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.

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