Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias
Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias
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DOI：
10.1073/pnas.070029997
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Fusco, A
中科院分区：
文献类型：
--
作者：
Scala, S;Portella, G;Fusco, A
高迁移率 I 类 (HMGI) 蛋白在多种人类恶性肿瘤中过度表达。我们之前证明，抑制 HMGI 合成可以防止甲状腺细胞转化。在这里，我们报道了一种以反义方向携带 HMGI(Y) 基因的腺病毒 (Ad-Yas) 诱导了两种人甲状腺间变性癌细胞系（ARO 和 FB-1）的程序性细胞死亡，但不诱导正常甲状腺细胞。 Ad-Yas 病毒导致肺癌、结肠癌和乳腺癌细胞死亡。携带 lacZ 基因的中央腺病毒不会抑制正常细胞或肿瘤细胞的生长。 Ad-Yas 对 ARO 细胞在无胸腺小鼠中诱导的肿瘤进行治疗，导致肿瘤部位急剧减少。因此，通过HMGI(Y)反义腺病毒载体抑制HMGI(Y)蛋白合成可能是多种人类恶性肿瘤的有效治疗策略，其中HMGI(Y)基因过度表达是常见事件。
High mobility group I (HMGI) proteins are overexpressed in several human malignant tumors. We previously demonstrated that inhibition of HMGI synthesis prevents thyroid cell transformation. Here, we report that an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) induced programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not normal thyroid cells. The Ad-Yas virus led to death of lung, colon, and breast carcinoma cells. A central adenovirus carrying the lacZ gene did not inhibit the growth of either normal or neoplastic cells. Ad-Yas treatment of tumors induced in athymic mice by ARO cells caused a drastic reduction in tumor site. Therefore, suppression of HMGI(Y) protein synthesis by an HMGI(Y) antisense adenoviral vector may be a useful treatment strategy in a variety of human malignant neoplasias, in which HMGI(Y) gene overexpression is a general event.