A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells
A serologically identified tumor antigen encoded by a homeobox gene promotes growth of ovarian epithelial cells
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DOI：
10.1073/pnas.071594398
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发表时间：
2001-03-27
影响因子：
11.1
通讯作者：
Roden, RBS
中科院分区：
文献类型：
--
作者：
Naora, H;Yang, Y;Roden, RBS
卵巢癌被认为是由卵巢表面上皮细胞产生的，其机制尚不清楚，与肿瘤相关的分子具有潜在的免疫原性，但很少有卵巢肿瘤抗原被鉴定出来。由于卵巢癌可引起患者的体液反应，我们通过免疫筛选卵巢癌患者血清的cDNA表达文库来寻找新的肿瘤抗原。分离到7个同源盒基因HOXB7对应的克隆，使用纯化的重组HOXB7蛋白进行elisa检测，39例卵巢癌患者中有13例对HOXB7有显著的血清学反应，29例健康女性中只有1例对HOXB7有显著的血清学反应（P < 0.0001）。在卵巢癌中发现HOXB7的表达水平明显高于正常卵巢表面上皮，提示患者体内HOXB7的免疫原性可能与其在卵巢癌中的表达升高有关，在永活正常卵巢表面上皮细胞中过表达HOXB7可显著促进细胞增殖，并且HOXB7过表达可增加细胞内碱性成纤维细胞生长因子的积累和分泌。这些结果表明HOXB7作为一种肿瘤抗原，其上调表达可能在促进卵巢癌的生长和发展中发挥重要作用。
Ovarian carcinomas are thought to arise from cells of the ovarian surface epithelium by mechanisms that are poorly understood, Molecules associated with neoplasia are potentially immunogenic, but few ovarian tumor antigens have been identified, Because ovarian carcinomas can elicit humoral responses in patients, we searched for novel tumor antigens by immunoscreening a cDNA expression library with ovarian cancer patient serum. Seven clones corresponding to the homeobox gene HOXB7 were isolated, ELISAs using purified recombinant HOXB7 protein revealed significant serologic reactivity to HOXB7 in 13 of 39 ovarian cancer patients and in only one of 29 healthy women (P < 0.0001). Ovarian carcinomas were found to express HOXB7 at markedly higher levels than normal ovarian surface epithelium, suggesting that immunogenicity of HOXB7 in patients could be associated with its elevated expression in ovarian carcinomas, Overexpression of HOXB7 in immortalized normal ovarian surface epithelial cells dramatically enhanced cellular proliferation, Furthermore, HOXB7 overexpression increased intracellular accumulation and secretion of basic fibroblast growth factor, a potent angiogenic and mitogenic factor, These results reveal HOXB7 as a tumor antigen whose up-regulated expression could play a significant role in promoting growth and development of ovarian carcinomas.