Antelman D, Machemer T, Huyghe B G, Shepard H M, Maneval D, Johnson D E
Canji Inc., San Diego, California 92121.
Oncogene. 1995 Feb 16;10(4):697-704.
Reconstitution of retinoblastoma gene (RB) deficient tumor cells with RB generally leads to growth suppression in vitro and/or reduced tumorigenicity in nude mice. An alternate approach to gene replacement is the delivery of the RB gene product (p110RB) into cells lacking its expression. In this report we demonstrate that exogenously added p110RB is taken up by and localized to the nucleus of cultured cells and has growth suppression properties similar to endogenous RB. RB-negative (RBneg) tumor cells are preferentially growth inhibited while most RB-positive (RBpos) tumor cells and normal cells are much less sensitive. We have extended these studies to relevant nude mouse xenograft models for human lung cancer. Local or systemic administration of p110RB inhibits tumor growth in treated animals. These results represent the first use of a tumor suppressor protein as a potential cancer therapeutic.
用视网膜母细胞瘤基因（RB）对RB缺陷的肿瘤细胞进行重组，通常会导致体外生长抑制和/或裸鼠致瘤性降低。基因替代的另一种方法是将RB基因产物（p110RB）导入缺乏其表达的细胞中。在本报告中，我们证明外源添加的p110RB被培养细胞摄取并定位于细胞核，并且具有与内源性RB相似的生长抑制特性。RB阴性（RBneg）肿瘤细胞优先受到生长抑制，而大多数RB阳性（RBpos）肿瘤细胞和正常细胞则不太敏感。我们已将这些研究扩展到相关的人肺癌裸鼠异种移植模型。局部或全身给予p110RB可抑制治疗动物的肿瘤生长。这些结果代表了首次将肿瘤抑制蛋白用作潜在的癌症治疗方法。
