Fernandez A, Fosdick L J, Marin M C, Diaz C, McDonnell T J, Ananthaswamy H N, McConkey D J
Department of Immunology, University of Texas MD Anderson Cancer Center, Houston 77030.
Oncogene. 1995 Feb 16;10(4):769-74.
Transfection of a murine fibroblast cell line with an activated form of the Harvey ras oncogene conferred sensitivity to apoptosis induced by various agents. This intrinsic sensitivity to apoptosis correlated with the expression of endogenous endonuclease activity in isolated nuclei that was undetectable in the untransfected parental cell line. Subsequent transfection with the human bcl-2 oncogene prevented the morphological and biochemical features of apoptosis in whole cells, although it failed to confer complete protection against cell death. Furthermore, transfection of the bcl-2 oncogene also inhibited the enhanced endonuclease activity in isolated nuclei. Our results indicate that some of the effects of Ha-ras and bcl-2 and potentially other oncogenes, are exerted on the biochemical machinery of apoptosis at the level of the nucleus.
用活化形式的哈维鼠肉瘤病毒癌基因（Harvey ras oncogene）转染小鼠成纤维细胞系，可使其对多种诱导剂诱导的细胞凋亡产生敏感性。这种对细胞凋亡的内在敏感性与分离细胞核中内源性核酸内切酶活性的表达相关，而在未转染的亲本细胞系中未检测到该活性。随后用人bcl-2癌基因进行转染，可防止全细胞中细胞凋亡的形态学和生化特征出现，尽管它未能完全保护细胞免于死亡。此外，bcl-2癌基因的转染还抑制了分离细胞核中增强的核酸内切酶活性。我们的结果表明，Ha-ras和bcl-2以及其他潜在癌基因的某些作用是在细胞核水平上作用于细胞凋亡的生化机制。
