Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
Selective toxicity of TGF-alpha-PE40 to EGFR-positive cell lines: selective protection of low EGFR-expressing cell lines by EGF.
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DOI：
10.1038/bjc.1994.194
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发表时间：
1994-06
影响因子：
8.8
通讯作者：
Harris, A. L.
中科院分区：
文献类型：
--
作者：
Kirk, J.;Carmichael, J.;Stratford, I. J.;Harris, A. L.
研究了人乳腺癌和肺癌细胞系对tgf - α - pe40的敏感性。tgf - α - pe40是一种新型的嵌合重组细胞毒素，由两个独立的结构域组成，(i) tgf - α和（ii）假单胞菌外毒素蛋白PE-40的40 kDa片段。毒性变化广泛，与表皮生长因子受体（EGFR）水平相关（P = 0.01）， EGF可显著降低其毒性，表明tgf - α - pe40与EGFR结合在介导毒性中起重要作用。EGFR表达水平低的细胞系受EGF的保护程度最高，表明正常（EGFR低表达）组织在体内可能受到EGF的选择性保护。p -糖蛋白不赋予对tgf - α - pe40的耐药性，并且毒性不受多药耐药调节剂（环孢素A、他莫昔芬、维拉帕米）的影响，这表明tgf - α - pe40在耐药肿瘤的临床管理中发挥作用。
The sensitivity of human breast and lung cancer cell lines to TGF-alpha-PE40, a novel chimeric recombinant cytotoxin composed of two independent domains, (i) TGF-alpha and (ii) a 40 kDa segment of the Pseudomonas exotoxin protein, PE-40, was investigated. Toxicity varied widely, correlated with epidermal growth factor receptor (EGFR) levels (P = 0.01) and was greatly reduced by EGF, indicating that binding of TGF-alpha-PE40 to EGFR is important in mediating toxicity. Cell lines expressing low EGFR levels were most highly protected by EGF, indicating that normal (low EGFR-expressing) tissue may be selectively protected by EGF in vivo. P-glycoprotein did not confer resistance to TGF-alpha-PE40, and toxicity was unaffected by multidrug resistance-modulating agents (cyclosporin A, tamoxifen, verapamil), indicating a role for TGF-alpha-PE40 in the clinical management of drug-resistant tumours.
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影响因子：
8.8
作者：
KIRK, J;HOULBROOK, S;CARMICHAEL, J
通讯作者：
CARMICHAEL, J
影响因子：
8.4
作者：
KOHLER, M;BAUKNECHT, T;WAGNER, E
通讯作者：
WAGNER, E
影响因子：
8.8
作者：
NICHOLSON, S;RICHARD, J;HARRIS, AL
通讯作者：
HARRIS, AL
影响因子：
8.4
作者：
BILOUS, M;MILLIKEN, J;MATHIJS, JM
通讯作者：
MATHIJS, JM
影响因子：
8.4
作者：
KIRK, J;HOULBROOK, S;CARMICHAEL, J
通讯作者：
CARMICHAEL, J