- 作者: 方剛; Limin Li; 施河
- 作者服務機構: 國立臺灣師範大學生物系; 美國德州大學安德生癌症中心細胞生物系
- 中文摘要: 本文以肺癌腺細胞為模式,探討上皮生長因子受體在轉移後的表現變異情形。非細小肺癌細胞株腺細胞DMS4C,由裸鼠頸動脈注入後,位於肺、脾、肝及腦轉移所出現腫瘤,將之處理培養後,形成不同細胞株。實驗結果顯示,上皮生長因子受體表現在轉移後,皆有不同程度的降低。上皮生長因子受體表現在肺、脾、肝及腦轉移細胞株分別降低70%,79%,85%及89%。其在脾、肝及腦轉移細胞株發展成與原始細胞完全不一樣的結合常數而且不具磷酸化特性的上皮生長因子受體。而衍生肺轉移細胞則沒有太多變化,這種現象告訴我們,肺癌細胞轉移時,不需依靠上皮生長因子受體增殖,而迴異於一般原始細胞的生長機制。
- 英文摘要: The metastatic variants of human lung adenocarcinoma cell line DMS4C were established by selec-tion in vivo. Lung, brain, spleen and liver metastatic tumors derived from intracarotid inoculation ofathymic BALB/c mice were collected, and their corresponding variant cell lines established. The epidermalerowth factor (EGF_ receptor expression of the the parental cell line as well as the metastatic variant celllines were investigated. I-labeled EGF binding assays showed tnat there were two types of EGF receptorsin both parental and metastatic variants. Compared to DMS4C, the EGF binding capacities were found tobe down-regulated by 70, 79, 85 and 89% for lung, spleen, liver and brain variant, respectively. The dis-sociation constants of spleen, liver and brain EGF receptors were distinct from that of the parental cellline. The EGF receptor autophosphorylation activity of lung variant was shown to be down-regulated asshown by immune complex kinase assay that corresponded to the reduced EGF receptor numbers whereaskinase activities of the liver, spleen and brain variants EGF receptors were completely abolished. However,the 170 kilodalton EGF receptor was shown to be unaltered during metastasis. The results indicated that,during metastasis progression, the proliferation of adenocarcinoma cells may have adopted a different growthregulation that is independent of EGF receptor kinase-modulated autocrine pathway. The result also impliesthat other oncogene may emerge as the major growth regulator for distant metastasis of adenocarcinomacancer cells. This work provides a model for understanding tumor metastasis progression of human lungcancer.
- 中文關鍵字: epidermal growth factor receptors; human lung cancer adenocarcinoma cells; metastasis.
- 英文關鍵字: --