Human pituitary tumor-transforming gene induces angiogenesis
Human pituitary tumor-transforming gene induces angiogenesis
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DOI：
10.1210/jc.86.2.867
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发表时间：
2001-02-01
影响因子：
5.8
通讯作者：
Melmed, S
中科院分区：
文献类型：
--
作者：
Ishikawa, H;Heaney, AP;Melmed, S
血管生成是肿瘤进展和转移的关键决定和限速步骤，由于垂体肿瘤转化基因(PTTG)可诱导碱性成纤维细胞生长因子(BFGF)，我们检测了过量表达野生型人PTTG的NIH-3T3细胞的条件培养液(CM)诱导的血管生成。我们还研究了PTTG在一系列人类肿瘤中的表达与肿瘤血管的关系。Wt-hPTTG转染人脐静脉内皮细胞的CM在体外可诱导人脐静脉内皮细胞的增殖、迁移和管状形成。与未转染的NIH-3T3细胞相比，WT-hPTTG-CM中的bFGF浓度(10.5+/-0.56)较未转染的CM(3.3+/-0.56pg/mL)高(P<；0.01)。在体内，浓缩的WT-hPTTG-CM诱导鸡绒毛膜尿囊膜轮状出现。此外，在PTTG的C末端富含Pro区域存在点突变的hPTTG-CM诱导的血管生成活性弱于WT-hPTTG-CM(P<；0.01)。因此，人PTTG在体外和体内血管生成模型中都能诱导血管生成表型，并且高PTTG信使核糖核酸与人类肿瘤的血管生成表型相关。这些PTTG导向的血管生成作用可能是通过碱性成纤维细胞生长因子介导的，碱性成纤维细胞生长因子也促进了肿瘤的生长。
Angiogenesis is a key determinant and rate-limiting step in tumor progression and metastatic spread, As pituitary tumor-transforming gene (PTTG) induces basic fibroblast growth factor (bFGF), we tested angiogenesis induced by conditioned medium (CM) derived from NIH-3T3 transfectants overexpressing wild-type human PTTG (WT-hPTTG-CM). We also examined the relationship between PTTG expression and tumor vascularity in a series of human tumors. CM from Wt-hPTTG transfectants induced proliferation, migration, and tube formation of human umbilical vein endothelial, cells in vitro. The bFGF concentration in WT-hPTTG-CM was elevated (10.5 +/- 0.56) compared with CM from nontransfected NIH-3T3 cells (3.3 +/- 0.56 pg/mL), and addition of anti-bFGF antibody to CM abrogated these angiogenesis markers (P < 0.01). In vivo, concentrated WT-hPTTG-CM induced chick chorioallantoic membrane spoke-wheel-like appearances. Moreover, CM derived from hPTTG transfectants harboring a point mutation on the C-terminus proline-rich region of PTTG induced weaker angiogenic activity than WT-hPTTG-CM (P < 0.01). Thus, human PTTG induces an angiogenic phenotype in both in vitro and in vivo angiogenesis models, and high PTTG messenger ribonucleic acid is associated with an angiogenic phenotype in human tumors. These PTTG-directed angiogenic actions may be mediated through bFGF, which also contributes to tumor growth.