Frisch S M, Dolter K E
La Jolla Cancer Research Foundation, California 92037, USA.
Cancer Res. 1995 Dec 1;55(23):5551-5.
We reported previously that the adenovirus E1a gene reversed the transformed phenotype of one human melanoma and one fibrosarcoma cell line (S. Frisch, Proc. Natl. Acad. Sci. USA, 88: 9077-9081, 1991). To determine the generality of the tumor suppression effects of E1a, a diversity of tumor cell lines, including A204 rhabdomyosarcoma, RD rhabdomyosarcoma, Saos-2 osteosarcoma, NCI-H23 non-small cell lung carcinoma, MDA-MB435S breast carcinoma, and ras-transformed MDCK kidney epithelial cells, were infected with a retrovirus bearing the 12S E1a coding sequence. We demonstrate here that the expression of E1a severely reduced the anchorage-independent and tumorigenic growth of these cell lines without affecting their growth under normal culture conditions. The parental tumor cells used in this study did not overexpress c-erbB-2/neu, and E1a did not affect its expression in these cells. Thus, tumor suppression by E1a can operate in a wide variety of human tumor cells by c-erbB-2/neu-independent mechanisms. E1a also sensitized these cell lines to the cytotoxic effects of the anticancer drugs etoposide and cisplatin. The results suggest that E1a could prove useful for the gene therapy of a wide variety of human cancers.
我们先前报道，腺病毒E1a基因可逆转一种人黑色素瘤细胞系和一种纤维肉瘤细胞系的转化表型（S. 弗里施，《美国国家科学院院刊》，88: 9077 - 9081, 1991）。为确定E1a肿瘤抑制作用的普遍性，用携带12S E1a编码序列的逆转录病毒感染了多种肿瘤细胞系，包括A204横纹肌肉瘤、RD横纹肌肉瘤、Saos - 2骨肉瘤、NCI - H23非小细胞肺癌、MDA - MB435S乳腺癌以及经ras转化的MDCK肾上皮细胞。我们在此证明，E1a的表达严重降低了这些细胞系的不依赖贴壁生长和致瘤性生长，而不影响它们在正常培养条件下的生长。本研究中使用的亲本肿瘤细胞未过表达c - erbB - 2/neu，且E1a不影响其在这些细胞中的表达。因此，E1a的肿瘤抑制作用可通过不依赖c - erbB - 2/neu的机制在多种人类肿瘤细胞中发挥作用。E1a还使这些细胞系对抗癌药物依托泊苷和顺铂的细胞毒性作用敏感。结果表明，E1a可能对多种人类癌症的基因治疗有用。
