Goto Yasufumi, Matsuzaki Yuriko, Kurihara Sachiko, Shimizu Ayako, Okada Tsutomu, Yamamoto Kazuhiko, Murata Hiroshi, Takata Minoru, Aburatani Hiroyuki, Hoon Dave S B, Saida Toshiaki, Kawakami Yutaka
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Shinanomachi, Tokyo, Japan.
Cancer Res. 2006 Apr 15;66(8):4443-9. doi: 10.1158/0008-5472.CAN-05-2505.
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.
鉴定在黑色素瘤细胞中优先表达并参与其恶性表型的分子，对于理解黑色素瘤生物学以及开发新的诊断和治疗方法至关重要。通过使用基因芯片比较黑色素瘤细胞系与各种正常组织的表达谱，并通过逆转录 - PCR、Northern印迹和Western印迹分析确认所选基因的实际表达，发现脂肪酸结合蛋白7（FABP7）在黑色素瘤中频繁表达。免疫组织化学检查显示，15个黑色素瘤组织中有11个表达FABP7。用FABP7特异性小干扰RNA下调FABP7表达后，六个黑色素瘤细胞系中有两个的体外细胞增殖和基质胶侵袭受到抑制。通过用FABP7 cDNA转染使FABP7在FABP7阴性的胚胎肾细胞系293T中过表达，导致细胞增殖和基质胶侵袭增强，表明FABP7在某些黑色素瘤细胞系的恶性表型中起作用。分别在25例黑色素瘤患者血清中的14例（56%）或31例中的8例（26%）中检测到对噬菌体或细菌重组FABP7蛋白特异的IgG抗体，但在健康个体血清中未检测到，表明FABP7是黑色素瘤患者中的一种免疫原性抗原。这些结果表明，FABP7在黑色素瘤中频繁表达，可能参与细胞增殖和侵袭，并且可能是诊断和治疗方法开发的潜在靶点。
