Effects of c-erbB2 overexpression on the drug sensitivities of normal human mammary epithelial cells
Effects of c-erbB2 overexpression on the drug sensitivities of normal human mammary epithelial cells
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DOI：
10.1093/jnci/92.12.987
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发表时间：
2000-06-21
期刊：
影响因子：
--
通讯作者：
Kohn, KW
中科院分区：
文献类型：
--
作者：
Orr, MS;O'Connor, PM;Kohn, KW
背景：编码酪氨酸激酶受体的c-erbB2基因在乳腺肿瘤中的过度表达与乳腺癌患者对各种治疗的反应增加或减少有关。在乳腺癌细胞系中，外源性c-erbB2的过度表达有时会改变药物敏感性，但有时没有影响。为了避免与已建立的癌细胞系相关的遗传复杂性，研究了正常人乳腺上皮细胞（HMECs），以确定c-erbB2本身过表达是否会改变化疗敏感性。方法：设计hmec过度表达c-erbB2，然后评估这些细胞的化学敏感性变化。结果：过度表达c-erbB2的HMECs对一组化疗药物的化学敏感性没有任何改变，这在细胞的生长曲线上显示为95%的置信区间，使用荧光激活的细胞分选对表面过度表达c-erbB2的HMECs进行富集，分离出85%的纯细胞群体并评估其化学敏感性。同样，这些细胞在化学敏感性方面没有表现出任何变化。结论：这些结果表明，c-erbB2过表达本身并不足以诱导化学敏感性的变化。使用正常人类细胞进行细胞研究，其中系统的复杂性可以通过添加一个，两个甚至更多与癌症发展相关的基因来仔细控制，这可能提供有关基因产物如何相互作用以及哪些组合在调节化学敏感性方面至关重要的有价值的信息。
Background: Overexpression of the gene c-erbB2, which encodes a receptor tyrosine kinase, in breast tumors has been linked with either increased or decreased response of breast cancer patients to various therapies. In breast cancer cell lines, overexpression of exogenous c-erbB2 sometimes alters drug sensitivities but sometimes has no effect. To avoid the genetic complexities associated with established cancer cell lines, normal human mammary epithelial cells (HMECs) were studied to determine whether c-erbB2 overexpression by itself would alter chemosensitivity. Methods: HMECs were designed to overexpress c-erbB2, and these cells were then evaluated for alterations in chemosensitivity. Results: HMECs overexpressing c-erbB2 failed to show any alterations in chemosensitivity to a panel of chemotherapeutic agents, as indicated by 95% confidence intervals on growth curves of cells treated with or without the agent of interest, With the use of fluorescence-activated cell sorting to enrich for HMECs overexpressing c-erbB2 on their surface, an 85% pure population of cells was isolated and their chemosensitivity was evaluated. Again, the cells failed to display any alterations in chemosensitivity. Conclusions: These results suggest that overexpression of c-erbB2 is not sufficient by itself to induce changes in chemosensitivity. Cellular studies using normal human cells in which the complexity of the system can be carefully controlled by the addition of one, two, or even more genes associated with cancer development may provide valuable information about how the products of the genes interact with each other and which combinations are critical in regulating chemosensitivity.