Iwamoto Y, Reich R, Nemeth G, Yamada Y, Martin G R
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda.
Clin Exp Metastasis. 1993 Nov;11(6):492-501. doi: 10.1007/BF00054940.
We transfected mouse 10T1/2 fibroblasts with the H-ras oncogene and isolated lines expressing H-ras. One of the lines exhibited a highly malignant phenotype with the ability to produce large tumors and to colonize the lung after tail vein injection. In addition, the cells of this line showed increased collagenase IV production, directed migration and invasiveness, properties associated with the ability of tumor cells to metastasize. Since cyclic adenosine 3',5'-monophosphate (cAMP) is known to down-regulate ras expression, we exposed the malignant cells (Cl-1) to either N6, 2',0-dibutyryl cAMP (DB-cAMP) or 8-bromo cAMP (8-Br-cAMP), either with or without a phosphodiesterase inhibitor. We found that these treatments reduced the expression of ras, chemotaxis, invasiveness, and lung colonization of the ras-transformed cells. We therefore postulate that the malignancy of some cells may be regulated by alterations in the intracellular cAMP levels by suppressing ras expression and/or by reducing other activities required for the dissemination of tumor cells.
我们用H-ras癌基因转染小鼠10T1/2成纤维细胞，并分离出表达H-ras的细胞系。其中一个细胞系表现出高度恶性的表型，能够产生大的肿瘤，并在尾静脉注射后在肺部形成转移灶。此外，该细胞系的细胞显示出Ⅳ型胶原酶产生增加、定向迁移和侵袭性，这些特性与肿瘤细胞转移的能力相关。由于已知环磷酸腺苷（cAMP）可下调ras表达，我们将恶性细胞（Cl-1）暴露于N6,2',0-二丁酰环磷腺苷（DB-cAMP）或8-溴环磷腺苷（8-Br-cAMP）中，同时或不同时使用磷酸二酯酶抑制剂。我们发现这些处理降低了ras的表达、趋化性、侵袭性以及ras转化细胞的肺转移能力。因此，我们推测某些细胞的恶性程度可能通过抑制ras表达和/或降低肿瘤细胞播散所需的其他活性，由细胞内cAMP水平的改变来调节。
