Boehm Jesse S, Hession Meghan T, Bulmer Sara E, Hahn William C
Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Dana 710C, Boston, MA 02115-6013, USA.
Mol Cell Biol. 2005 Aug;25(15):6464-74. doi: 10.1128/MCB.25.15.6464-6474.2005.
Murine embryo fibroblasts are readily transformed by the introduction of specific combinations of oncogenes; however, the expression of those same oncogenes in human cells fails to convert such cells to tumorigenicity. Using normal human and murine embryonic fibroblasts, we show that the transformation of human cells requires several additional alterations beyond those required to transform comparable murine cells. The introduction of the c-Myc and H-RAS oncogenes in the setting of loss of p53 function efficiently transforms murine embryo fibroblasts but fails to transform human cells constitutively expressing hTERT, the catalytic subunit of telomerase. In contrast, transformation of multiple strains of human fibroblasts requires the constitutive expression of c-Myc, H-RAS, and hTERT, together with loss of function of the p53, RB, and PTEN tumor suppressor genes. These manipulations permit the development of transformed human fibroblasts with genetic alterations similar to those found associated with human cancers and define specific differences in the susceptibility of human and murine fibroblasts to experimental transformation.
通过导入特定组合的癌基因，鼠胚胎成纤维细胞很容易被转化；然而，相同的癌基因在人类细胞中的表达却无法使这些细胞具有致瘤性。利用正常的人类和鼠胚胎成纤维细胞，我们发现，与转化可比的鼠细胞相比，人类细胞的转化需要一些额外的改变。在p53功能缺失的情况下导入c-Myc和H-RAS癌基因可有效转化鼠胚胎成纤维细胞，但无法转化组成型表达端粒酶催化亚基hTERT的人类细胞。相比之下，多种人类成纤维细胞系的转化需要c-Myc、H-RAS和hTERT的组成型表达，以及p53、RB和PTEN肿瘤抑制基因功能的缺失。这些操作使得能够培育出具有与人类癌症相关的类似基因改变的转化人类成纤维细胞，并明确了人类和鼠成纤维细胞对实验性转化易感性的特定差异。
