Wyllie A H, Rose K A, Morris R G, Steel C M, Foster E, Spandidos D A
Department of Pathology, University Medical School, Edinburgh, UK.
Br J Cancer. 1987 Sep;56(3):251-9. doi: 10.1038/bjc.1987.186.
The effects of expression of human c-myc and both mutated (T24) and normal forms of human Ha-ras-1 were studied in an aneuploid rat fibroblast line (208F). Mutated T24 Ha-ras was also studied in a near-diploid cell derived from early passage Chinese hamster lung fibroblasts (CHL). In contrast to the parental fibroblasts, cells expressing any of the human oncogenes engendered rapidly growing tumours in immune-suppressed animals. Blood- and lymph-borne metastases were observed from both ras- and myc-expressing cells. In general ras-expressing cells were more aggressive than those expressing myc. In the 208F background, expression of c-myc was associated with an incidence of mitosis similar to that in tumours expressing T24 Ha-ras, but incidence of single cell death by apoptosis was higher. Quantitatively, expression of human oncogene mRNA was constant during growth in vivo, and similar to that sometimes observed in human neoplasms. Of 9 endogenous proto-oncogenes, 7 showed no change in expression from the parental fibroblasts, but c-abl and c-fos were strongly expressed in all cells expressing human ras or myc. Thus these tumorigenic cells, although transfected with single human oncogenes, all expressed oncogenes with both nuclear- and membrane-associated products.
在一个非整倍体大鼠成纤维细胞系（208F）中研究了人类c-myc以及人类Ha-ras-1的突变型（T24）和正常型的表达效应。突变型T24 Ha-ras也在源自早期传代中国仓鼠肺成纤维细胞（CHL）的近二倍体细胞中进行了研究。与亲代成纤维细胞不同，表达任何一种人类癌基因的细胞在免疫抑制动物中都会引发快速生长的肿瘤。观察到表达ras和myc的细胞都出现了血行和淋巴转移。一般来说，表达ras的细胞比表达myc的细胞更具侵袭性。在208F背景下，c-myc的表达与有丝分裂发生率相关，类似于表达T24 Ha-ras的肿瘤，但通过凋亡导致的单细胞死亡发生率更高。从数量上看，人类癌基因mRNA的表达在体内生长过程中保持恒定，并且与在人类肿瘤中有时观察到的情况相似。在9个内源性原癌基因中，7个与亲代成纤维细胞相比表达没有变化，但c-abl和c-fos在所有表达人类ras或myc的细胞中均强烈表达。因此，这些致瘤细胞虽然仅转染了单个人类癌基因，但都表达了具有核相关和膜相关产物的癌基因。
