Li J J, Friedman-Kien A E, Cockerell C, Nicolaides A, Liang S L, Huang Y Q
Department of Microbiology and Medicine, NYU Medical Center, New York 10016, USA.
J Cancer Res Clin Oncol. 1998;124(5):259-64. doi: 10.1007/s004320050163.
Recently, the expression of fibroblast growth factor 3 (FGF3) was found in 55% of human Kaposi's sarcoma (KS) tumor tissues examined, while almost no expression of FGF3 was found in normal skin. To further these studies, human FGF3 cDNA were constructed by the overlap-extension method. The proteins translated from two FGF3 cDNA, which differ only in the sequences preceding the AUG presumed to be the initiation codon, were shown to have the same molecular mass. This result suggests that translation of human FGF3, which is different from mouse FGF3, begins only at the AUG site. The human FGF cDNA was transfected into NIH3T3 cells. The NIH 3T3 cells transformed by FGF3 were then injected subcutaneously into athymic nude mice. Nodular lesions developed at the injection sites in all seven mice injected with the F3-1 cell clone, which showed high expression of FGF3, and in two out of six mice injected with the F3-2 cell clone, which expressed a low level of FGF3. Histopathological features of these tumors contained fascicles of spindle-shaped cells surrounding irregular endothelial lined vascular clefts, similar to those observed in human KS lesions. Immunohistochemical staining for factor V111 antigen revealed reactivity in multiple areas, especially in abundant vascular structures of the tumor sections examined. The expression of FGF3 together with the FGF receptors FGFR1, FGFR2, and FGFR3, was detected in the mouse tumors by Northern blot analysis. Our results indicate that tumors induced by FGF3-transformed NIH3T3 cells show some similarities to human KS tumors. In conclusion, our results demonstrate the potential tumorigenic and angiogenic role of human FGF3.
最近，在检测的55%的人类卡波西肉瘤（KS）肿瘤组织中发现了成纤维细胞生长因子3（FGF3）的表达，而在正常皮肤中几乎未发现FGF3的表达。为了进一步开展这些研究，通过重叠延伸法构建了人类FGF3 cDNA。从两个仅在推测为起始密码子的AUG之前的序列不同的FGF3 cDNA翻译而来的蛋白质，显示具有相同的分子量。这一结果表明，与小鼠FGF3不同的人类FGF3的翻译仅起始于AUG位点。将人类FGF cDNA转染到NIH3T3细胞中。然后将经FGF3转化的NIH 3T3细胞皮下注射到无胸腺裸鼠体内。在注射了高表达FGF3的F3-1细胞克隆的所有7只小鼠以及注射了低水平表达FGF3的F3-2细胞克隆的6只小鼠中的2只的注射部位出现了结节性病变。这些肿瘤的组织病理学特征包括围绕不规则内皮衬里血管裂隙的梭形细胞束，类似于在人类KS病变中观察到的特征。对因子VIII抗原的免疫组织化学染色显示在多个区域有反应性，特别是在所检查的肿瘤切片的丰富血管结构中。通过Northern印迹分析在小鼠肿瘤中检测到了FGF3以及FGF受体FGFR1、FGFR2和FGFR3的表达。我们的结果表明，由FGF3转化的NIH3T3细胞诱导的肿瘤与人类KS肿瘤有一些相似之处。总之，我们的结果证明了人类FGF3潜在的致瘤和血管生成作用。
