脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤...脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。展开更多
It is suggested that Δ6 fatty acid desaturase(FAD) plays a critical role in the biosynthesis of polyunsaturated fatty acids in plants and microalgae. But why does it adapt to the changed environments such as nitrogen...It is suggested that Δ6 fatty acid desaturase(FAD) plays a critical role in the biosynthesis of polyunsaturated fatty acids in plants and microalgae. But why does it adapt to the changed environments such as nitrogen starvation is seldom understood. One Δ6 FAD gene( MiD6 fad) from an arachidonic acidrich microalga M yrmecia incisa Reisigl(Chlorophyta) was first heterologously expressed in S accharomyces cerevisiae for the identification of function. The fatty acid profile of transgenic yeast detected by gas chromatography-mass spectrometry illustrated that the enzyme MiD6 FAD could convert linoleic and ?-linolenic acids to γ-linolenic and stearidonic acids, respectively, demonstrating that M iD6 fad encoded a Δ6 FAD. A 1 965-bp fragment of the cloned 2 347-bp 5′-upstream region of M iD6 fad was next subcloned and fused upstream with green fluorescent protein(GFP) gene to replace the GAL1 promoter of the vector pYES2. The generated construct was transformed into S. cerevisiae for function determination. Confocal microscopic images of the transformed line illustrated that this inserted fragment could drive GFP expression, which was further verified by fluorescence intensity quantification and Western blot analysis using antiGFP antibody. The conversion efficiency(approximately 2%-3%) of MiD6 FAD was much lower than the reported ? 3 FAD and Δ6 elongase in this microalga, suggesting that MiD6 FAD catalysed the possible ratelimiting step for ArA biosynthesis. The presence of several putative c is-acting regulatory elements in this identified promoter sheds new light on the regulation mechanism research of Δ6 FAD transcription for the ArA production in M. incisa in changing environmental factors.展开更多
目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色...目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色法检测125例脑星型细胞瘤组织中FABP5及CRABP2蛋白表达。全反式维甲酸作用前后,以Brdu-ELISA法检测胶质瘤细胞增殖,并以实时荧光定量PCR检测胶质瘤细胞株中FABP5及CRABP2在m RNA水平的表达。结果 FABP5阳性细胞比例在WHOⅡ级星型细胞瘤中占(16±9)%,Ⅲ级中占(33±22)%,Ⅳ级中占(50±29)%,FABP5蛋白表达与胶质瘤病理级别呈显著正相关(P<0.05)。CRABP2阳性细胞比例在Ⅱ级星型细胞瘤中占(46±12)%,WHOⅢ级中占(30±15)%,Ⅳ级中占(10±9)%,CRABP2蛋白表达与胶质瘤病理级别呈显著负相关(P<0.05)。全反式维甲酸促进了胶质瘤细胞株的增殖,全反式维甲酸作用后胶质瘤细胞FABP5 m RNA表达显著上调,而CRABP2显著下调。结论 FABP5及CRABP2的异常表达与胶质瘤恶性程度相关,并可能介导了胶质瘤细胞对维甲酸的分化抵抗效应。展开更多
In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal tr...In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state.The detailed route of this signal transduction pathway can be described as follows:when FABP5 expression is increased as the increasing malignancy,excessive amounts of fatty acids from intra-and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ).The phosphorylated or biologically activated PPARγthen modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis.Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice,a seven-fold reduction of tumour incidence,and a 100%reduction of metastasis rate.Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both in vitro and in nude mouse.These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.展开更多
文摘脂肪酸结合蛋白5(fatty acid binding protein 5,FABP5)是脂肪酸结合蛋白家族之一,在调控脂肪酸的摄取、运输和代谢中发挥重要作用。近年来多项研究证实,FABP5在多种肿瘤中高表达,其参与了肿瘤的增殖、转移以及诱导免疫逃逸等多种肿瘤生物学过程。该文综述了FABP5在肿瘤中的最新研究进展,旨在讨论FABP5在肿瘤中的作用及机制,为肿瘤相关研究提供新思路,同时为肿瘤新靶点的开发提供更多理论依据。
基金Supported by the National Natural Science Foundation of China(No.31172389)the Special Project of Marine Renewable Energy from the State Oceanic Administration(No.SHME2011SW02)the Shanghai Universities Peak Discipline Project of Aquaculture
文摘It is suggested that Δ6 fatty acid desaturase(FAD) plays a critical role in the biosynthesis of polyunsaturated fatty acids in plants and microalgae. But why does it adapt to the changed environments such as nitrogen starvation is seldom understood. One Δ6 FAD gene( MiD6 fad) from an arachidonic acidrich microalga M yrmecia incisa Reisigl(Chlorophyta) was first heterologously expressed in S accharomyces cerevisiae for the identification of function. The fatty acid profile of transgenic yeast detected by gas chromatography-mass spectrometry illustrated that the enzyme MiD6 FAD could convert linoleic and ?-linolenic acids to γ-linolenic and stearidonic acids, respectively, demonstrating that M iD6 fad encoded a Δ6 FAD. A 1 965-bp fragment of the cloned 2 347-bp 5′-upstream region of M iD6 fad was next subcloned and fused upstream with green fluorescent protein(GFP) gene to replace the GAL1 promoter of the vector pYES2. The generated construct was transformed into S. cerevisiae for function determination. Confocal microscopic images of the transformed line illustrated that this inserted fragment could drive GFP expression, which was further verified by fluorescence intensity quantification and Western blot analysis using antiGFP antibody. The conversion efficiency(approximately 2%-3%) of MiD6 FAD was much lower than the reported ? 3 FAD and Δ6 elongase in this microalga, suggesting that MiD6 FAD catalysed the possible ratelimiting step for ArA biosynthesis. The presence of several putative c is-acting regulatory elements in this identified promoter sheds new light on the regulation mechanism research of Δ6 FAD transcription for the ArA production in M. incisa in changing environmental factors.
文摘目的探讨脂肪酸结合蛋白5(fatty acid-binding protein 5,FABP5)与细胞维甲酸结合蛋白2(cellular retinoic acid-binding protein 2,CRABP2)在脑胶质瘤中的表达及与脑胶质瘤病理级别、维甲酸治疗抵抗的关系。方法应用免疫组织化学染色法检测125例脑星型细胞瘤组织中FABP5及CRABP2蛋白表达。全反式维甲酸作用前后,以Brdu-ELISA法检测胶质瘤细胞增殖,并以实时荧光定量PCR检测胶质瘤细胞株中FABP5及CRABP2在m RNA水平的表达。结果 FABP5阳性细胞比例在WHOⅡ级星型细胞瘤中占(16±9)%,Ⅲ级中占(33±22)%,Ⅳ级中占(50±29)%,FABP5蛋白表达与胶质瘤病理级别呈显著正相关(P<0.05)。CRABP2阳性细胞比例在Ⅱ级星型细胞瘤中占(46±12)%,WHOⅢ级中占(30±15)%,Ⅳ级中占(10±9)%,CRABP2蛋白表达与胶质瘤病理级别呈显著负相关(P<0.05)。全反式维甲酸促进了胶质瘤细胞株的增殖,全反式维甲酸作用后胶质瘤细胞FABP5 m RNA表达显著上调,而CRABP2显著下调。结论 FABP5及CRABP2的异常表达与胶质瘤恶性程度相关,并可能介导了胶质瘤细胞对维甲酸的分化抵抗效应。
文摘In this short communication,a novel fatty acid-binding protein 5(FABP5)-related signal transduction pathway in prostate cancer is reviewed.In castration-resistant prostate cancer(CRPC)cells,the FABP5-related signal transduction pathway plays an important role during transformation of the cancer cells from androgen-dependent state to androgen-independent state.The detailed route of this signal transduction pathway can be described as follows:when FABP5 expression is increased as the increasing malignancy,excessive amounts of fatty acids from intra-and extra-cellular sources are transported into the nucleus of the cancer cells where they act as signalling molecules to stimulate their nuclear receptor peroxisome proliferator-activated receptor gamma(PPARγ).The phosphorylated or biologically activated PPARγthen modulates the expression of its downstream target regulatory genes to trigger a series of molecular events that eventually lead to enhanced tumour expansion and aggressiveness caused by an overgrowth of the cancer cells with a reduced apoptosis and an increased angiogenesis.Suppressing the FABP5-related pathway via RNA interference against FABP5 has produced a 63-fold reduction in the average size of the tumours developed from CRPC cells in nude mice,a seven-fold reduction of tumour incidence,and a 100%reduction of metastasis rate.Experimental treatments of CRPC with novel FABP5 inhibitors have successfully inhibited the malignant progression of CRPC cells both in vitro and in nude mouse.These studies suggest that FABP5-related signal transduction pathway is a novel target for therapeutic intervention of CRPC cells.
