Glenn J, McDonald D, Horetsky R L, Sexton F M
Department of Surgery, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
J Surg Res. 1988 Apr;44(4):382-90. doi: 10.1016/0022-4804(88)90180-1.
DNAs of cell lines derived from human metastatic tumors were transfected into tumorigenic, nonmetastasizing murine cells (BALB 3T12-3) to determine if the capacity to metastasize could be conferred by this transfer of portions of the human genome. Using the calcium phosphate method, whole cell DNA was cotransfected into the murine cells along with a neomycin-resistance gene. Recipient murine cells (10(6] which grew in neomycin, indicating successful transfection, were injected via tail vein into 4- to 6-week-old male athymic nude mice. Animals were sacrificed if they appeared ill or at times up to 24 weeks after injection if they remained healthy. Murine cells transfected with DNA from one cell line derived from a hepatic metastasis of a human pancreatic adenocarcinoma (NCI-ZRY) formed experimental pulmonary metastases in 11 of 13 animals injected. Neither murine cells (unmanipulated BALB 3T12-3 cells) nor murine cells transfected with DNA from the same cell type (BALB 3T12-3 cells transfected with BALB 3T12-3 DNA) produced experimental metastases when each cell type was injected into 20 and 10 animals, respectively (P2 less than 0.0001). The results are consistent with the hypothesis that expression of a structural or regulatory protein encoded on human DNA conferred the metastatic phenotype to the recipient murine cells.
将源自人类转移性肿瘤的细胞系的DNA转染到具有致瘤性、无转移能力的小鼠细胞（BALB 3T12-3）中，以确定通过这种人类基因组部分的转移是否可以赋予转移能力。使用磷酸钙法，将全细胞DNA与新霉素抗性基因一起共转染到小鼠细胞中。在新霉素中生长的受体小鼠细胞（10⁶个）表明转染成功，通过尾静脉注射到4至6周龄的雄性无胸腺裸鼠中。如果动物出现疾病则将其处死，或者如果它们保持健康，则在注射后长达24周时处死。用源自人类胰腺腺癌肝转移灶的一个细胞系（NCI-ZRY）的DNA转染的小鼠细胞，在13只注射动物中的11只中形成了实验性肺转移。当分别将每种细胞类型注射到20只和10只动物中时，未处理的BALB 3T12-3细胞（未处理的小鼠细胞）或用相同细胞类型的DNA转染的小鼠细胞（用BALB 3T12-3 DNA转染的BALB 3T12-3细胞）均未产生实验性转移（P2小于0.0001）。这些结果与以下假设一致，即人类DNA编码的结构或调节蛋白的表达赋予了受体小鼠细胞转移表型。
