A new melanoma antigen fatty acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy
A new melanoma antigen fatty acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy
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DOI：
10.1158/0008-5472.can-05-2505
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发表时间：
2006-04-15
期刊：
影响因子：
11.2
通讯作者：
Kawakami, Y
中科院分区：
文献类型：
--
作者：
Goto, Y;Matsuzaki, Y;Kawakami, Y
发现在黑色素瘤细胞中优先表达并参与其恶性表型的分子对于了解黑色素瘤的生物学特性和开发新的诊断和治疗方法具有重要意义。通过比较黑色素瘤细胞株和正常组织的基因表达谱，并通过逆转录-聚合酶链式反应和Northern和Western印迹分析证实所选基因的真实表达，鉴定出在黑色素瘤中频繁表达的脂肪酸结合蛋白7(FABP7)。免疫组织化学检测15例黑色素瘤组织中有11例表达FABP7。通过FABP7特异性小干扰RNA下调FABP7的表达，在体外6个黑色素瘤细胞系中有2个的细胞增殖和Matrigel侵袭受到抑制。FABP7基因在FABP7阴性的胚胎肾细胞系293T中过表达，可促进细胞增殖和Matrigel侵袭，提示FABP7在某些黑色素瘤细胞系的恶性表型中起一定作用。在25例黑色素瘤患者和31例黑色素瘤患者血清中，分别有14例(56%)和8例(26%)检测到针对噬菌体和细菌重组FABP7蛋白的抗体，而正常人血清中未检测到该抗体。这些结果表明，FABP7在黑色素瘤中频繁表达，可能参与细胞的增殖和侵袭，可能是开发诊断和治疗方法的潜在靶点。
The identification of molecules that are preferentially expressed in melanoma cells and involved in their malignant phenotypes is important for understanding melanoma biology and the development of new diagnostic and therapeutic methods. By comparing the expression profile of a melanoma cell line with those of various normal tissues using GeneChip and by confirming the actual expression of the selected genes by reverse transcription-PCR and Northern and Western blot analyses, fatty acid-binding protein 7 (FABP7), which is frequently expressed in melanomas, was identified. Immunohistochemical examination revealed that FABP7 was expressed in 11 of 15 melanoma tissues. By down-regulating the FABP7 expression with FABP7-specific small interfering RNAs, in vitro cell proliferation and Matrigel invasion were suppressed in two of six melanoma cell lines. Overexpression of FABP7 in a FABP7-negative embryonic kidney cell line 293T by transfecting with the FABP7 cDNA resulted in enhanced cell proliferation and Matrigel invasion, indicating that FABP7 plays a role in the malignant phenotype of some melanoma cell lines. IgG antibodies specific for the phage or bacterial recombinant FABP7 protein were detected in 14 of 25 (56%) or in 8 of 31 (26%) sera from melanoma patients, respectively, but not in sera from healthy individuals, indicating that FABP7 is an immunogenic antigen in melanoma patients. These results showed that FABP7 is frequently expressed in melanoma, may be involved in cell proliferation and invasion, and may be a potential target for development of diagnostic and therapeutic methods.