MCF-7 BREAST-CANCER CELLS OVEREXPRESSING TRANSFECTED C-ERBB-2 HAVE AN IN-VITRO GROWTH ADVANTAGE IN ESTROGEN-DEPLETED CONDITIONS AND REDUCED ESTROGEN-DEPENDENCE AND TAMOXIFEN-SENSITIVITY IN-VIVO
MCF-7 BREAST-CANCER CELLS OVEREXPRESSING TRANSFECTED C-ERBB-2 HAVE AN IN-VITRO GROWTH ADVANTAGE IN ESTROGEN-DEPLETED CONDITIONS AND REDUCED ESTROGEN-DEPENDENCE AND TAMOXIFEN-SENSITIVITY IN-VIVO
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DOI：
10.1007/bf00665783
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发表时间：
1995-05-01
影响因子：
3.8
通讯作者：
KERN, FG
中科院分区：
文献类型：
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作者：
LIU, YL;ELASHRY, D;KERN, FG
将c-erbB-2表达载体转染到雌激素受体阳性（ER+）MCF-7人乳腺癌细胞系中，以确定这种跨膜酪氨酸激酶的过表达是否会增加该细胞系的恶性表型。当细胞在含有雌激素的培养基中进行时，观察到转染的c-erbB-2表达的损失。通过在无雌激素条件下连续保持转染的细胞系，可以获得在SKBR-3（一种由于基因扩增而过表达c-erbB-2的乳腺癌细胞系）中观察到的稳定过表达185 kDa c-erbB-2水平的均一群体。组成型激活c-erbB-2的水平各不相同的克隆分离株。尽管一些过表达细胞系确实在不补充雌激素的卵巢切除裸小鼠以及接受抗雌激素他莫昔芬的小鼠中获得了形成短暂肿瘤结节的能力，但一种表现出最高水平的组成性激活c-erbB-2的细胞系能够在两种条件下形成更大尺寸的静态肿瘤。相同的细胞系在补充雌激素的小鼠中形成了逐渐生长的肿瘤，其比注射对照细胞系的小鼠中观察到的肿瘤大得多，并且还显示出体外对抗雌激素的敏感性降低，但它仍然具有低转移表型。这些结果表明，c-erbB-2酪氨酸激酶介导的信号转导可以部分克服雌激素依赖性的ER+乳腺癌细胞的生长和c-erbB-2过表达赋予这样的细胞在雌激素的情况下的选择性优势。
A c-erbB-2 expression vector was transfected into the estrogen receptor positive (ER+)MCF-7 human breast cancer cell line to determine if overexpression of this transmembrane tyrosine kinase could increase the malignant phenotype of this cell line. Loss of transfected c-erbB-2 expression was observed when cells were carried in medium containing estrogen. Homogeneous populations stably overexpressing levels of the 185 kDa c-erbB-2 observed in the SKBR-3 a breast cancer cell line which overexpresses c-erbB-2 as a result of gene amplification could be obtained by continually maintaining the transfected cell lines in estrogen-free conditions. Levels of constitutively activated c-erbB-2 varied among clonal isolates. Whereas some overexpressing lines did acquire the ability to form transient tumor nodules in ovariectomized nude mice without estrogen supplementation, as well as in mice that received the antiestrogen tamoxifen, one cell line that exhibited the highest levels of constitutively activated c-erbB-2 was able to form static tumors of a larger size under both conditions. This same cell line formed progressively growing tumors in estrogen-supplemented mice that were much larger than observed in mice injected with control cell lines, and also showed reduced sensitivity to antiestrogens in vitro, but it continued to have a low metastatic phenotype. These results suggest that signal transduction mediated by the c-erbB-2 tyrosine kinase can partially overcome the estrogen dependence of ER+ breast cancer cells for growth and that c-erbB-2 overexpression confers a selective advantage to such cells in the absence of estrogen.