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Elevation of Epidermal Growth Factor Receptor Expression in a Brain-Metastasized Human Squamous Lung Cancer Cell Line

人類肺癌扁平細胞在腦移轉後表皮生長因子受體的異常變化

摘要


人類肺癌細胞中以扁平細胞最具移轉能力。本文在以肺癌扁平細胞為模式,探討表皮生長因子受體(EGF receptor)在移轉前後的表型變化。將非小細胞肺癌細胞株(NSCLC)NCI-H226(H226)由裸鼠頸動脈注入,使之產生腦移轉腫瘤後加以培養成細胞株。實驗結果顯示EGF receptor於腦移轉後在細胞表面有增加的現象,但EGF receptor本身所應具之磷酸化反應及對轉形生長因子-α(TGF-α)刺激反應卻有降低的趨勢,這種現象可能說明了人類肺癌扁平細胞在腦移轉之後不再侷限於早期細胞生長所需由TGF-α所引導之自身促激反應(autocrine),而可能由其它反應機制所取代。

並列摘要


The metastatic variant of human squamous cell cell line NCI-H226 (H226) was established by selection in vivo and its brain metastatic variant cell line H226B was examined. TGF-α increased cell proliferation of parental cell line H226 at an optimal concentration of 5 ng/ml, whereas H226B was less responsive to exogenous TGF-α (0.2 ng/ml - 100 ng/ml) in the assay. I^125-EGF binding assays showed that H226B has two types of EGF receptors, whereas H226 has only one type of EGF receptor. H226B cells have twice as many EGF receptors as that of H226. The kinase activity of H226B EGF receptors is down-regulated as shown by the immune complex assay. The brain metastaic variant H226 has an altered autocrine growth machanism compared to the parental cell line H226. This work provides a model for understanding the molecular events during tumor metastasis progression.

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