The effect of arachidonic acid on TNF-α-induced NF-κB signaling studied in human breast cancer cell line and rat mammary tumors

• Main Authors: Shang-Jung Cheng, 鄭上容
• Other Authors: 蘇慧敏
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/41085729172541047932

碩士 === 國立臺灣大學 === 生理學研究所 === 98 === Our Lab previous found that arachidonic acid (AA, 20:4n-6) levels are 10 times higher in mammary tumor tissue than in the normal mammary gland, and are positively correlated with the tumor weight. However, the mechanism is not clear. We then proposed AA may enhance nuclear factor kappaB (NF-κB) activation studied in human breast cancer cell line MCF-7 and rat mammary tumors. We hypothesized that AA enhanced tumor necrosis factor-α (TNF-α)-induced NF-κB signaling for the growth of the breast cancer cells. We also studied the correlation between NF-κB signaling and tumor weight in rat mammary tumor. MCF-7 cells were pretreated with 0, 10, 50 and 100 μM AA for 48 hours, and then were stimulated with TNF-α. Western blot analysis was performed on whole cell lysates, cytosol and nuclear fractions for the NF-κB signaling protein expression. AA supplementation resulted in increasing pAkt /Akt levels, IκBα degradation, nuclear p65 expression and reduced cyclin D1 expression in MCF-7. In study of rat mammary tumors, the tumor weight were positively correlated with pAkt/Akt ratio (r=0.6993, p=0.0009), were inversely correlated with IκBα expression (r=0.5319, p= 0.0751), were positively correlated with nuclear p65 expression (r=0.6282, p=0.0287) and were inversely correlated with cyclin D1 expression (r=0.7652, p <0.0001) in the mammary tumor. It was concluded that AA enhanced Akt signaling resulted in increasing IκBα degradation and nuclear p65 expression for the growth of breast cancer.