Fung Y K, T'Ang A, Murphree A L, Zhang F H, Qiu W R, Wang S W, Shi X H, Lee L, Driscoll B, Wu K J
Division of Hematology/Oncology, Childrens Hospital, Los Angeles, CA.
Oncogene. 1993 Oct;8(10):2659-72.
The suppression of tumor formation, first demonstrated by somatic cell hybrid and microcell fusion experiments, suggests the existence of a class of genes that selectively suppress the growth of tumor cells but not normal cells. The reintroduction of these genes into tumor cells presumably renders the cells responsive to in vivo growth inhibitory environment. As the inheritance of a defective retinoblastoma gene (Rb-1) allele results in a predisposition to the development of various cancers, and since inactivation of both alleles are observed in tumor cells, the Rb gene has been suspected to have the ability to suppress tumor growth. Data presented here demonstrated that different types of normal cells, which have a limited life span, were also growth arrested by a transfected Rb gene. Cell lines which are resistant to the growth suppression effect of the Rb gene in vitro, retain the ability to form tumors in nude mice even in the presence of a stable and highly expressed wild type Rb protein. We conclude that while the Rb gene can suppress the growth of many tumor cell lines, its growth suppression effect is not tumor specific.
体细胞杂交和微细胞融合实验首次证明了肿瘤形成的抑制作用，这表明存在一类基因，它们能选择性地抑制肿瘤细胞而非正常细胞的生长。将这些基因重新导入肿瘤细胞可能会使细胞对体内生长抑制环境产生反应。由于视网膜母细胞瘤基因（Rb-1）等位基因的缺陷遗传会导致易患各种癌症，并且在肿瘤细胞中观察到两个等位基因均失活，因此怀疑Rb基因具有抑制肿瘤生长的能力。此处呈现的数据表明，寿命有限的不同类型正常细胞也会因转染的Rb基因而生长停滞。在体外对Rb基因的生长抑制作用具有抗性的细胞系，即使在存在稳定且高表达的野生型Rb蛋白的情况下，仍保留在裸鼠中形成肿瘤的能力。我们得出结论，虽然Rb基因可以抑制许多肿瘤细胞系的生长，但其生长抑制作用并非肿瘤特异性的。
