Genetic and epigenetic alterations of the estrogen receptor gene and hormone independence in human breast cancer
Genetic and epigenetic alterations of the estrogen receptor gene and hormone independence in human breast cancer
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DOI：
10.1159/000055254
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发表时间：
1998-01-01
期刊：
影响因子：
3.5
通讯作者：
Kobayashi, S
中科院分区：
文献类型：
--
作者：
Iwase, H;Omoto, Y;Kobayashi, S
激素非依赖性肿瘤的存在是目前乳腺癌内分泌治疗的一个重大问题。雌激素受体（ER）基因突变可以改变蛋白质的生化活性，并可以影响激素反应性。然而，在乳腺癌中已经描述了相当多的重要突变。最近，在 mRNA 水平上检测到了许多变异的 ER，它们具有选择性剪接，产生外显子 3、5 或 7 的缺失。由变异 mRNA 诱导的截短的 ER 蛋白主要通过对正常 ER 蛋白的显性负作用而表现出抑制蛋白的作用。然而，激素依赖性丧失的机制仍然非常复杂。需要进一步评估临床行为和 ER 变异之间的相关性，以确定这些变异是否在激素抵抗性疾病中发挥作用。此外，ER 基因本身的 DNA 甲基化可能控制 ER 的表达。这些表观遗传变化在乳腺癌激素依赖的丧失中发挥着重要作用。
The existence of hormone-independent tumors is a substantial problem for the present endocrine treatment of breast cancers. Estrogen receptor (ER) gene mutation can change the biochemical activity of the protein and can affect hormone responsiveness. However, quite a few mutations of significance have been described in breast cancer. Recently, numerous variant ERs have been detected at the mRNA level with alternative splicing, yielding deletion of exon 3, 5, or 7. The truncated ER protein induced from variant mRNA could mainly be exhibited as a repressor through dominant negative effects on normal ER protein. The mechanism of the loss of hormone dependency is, however, still very complex. Further work to assess the correlation between clinical behavior and ER variants is required to determine whether these variants play a role in hormone-resistant disease. Additionally, the DNA methylation of the ER gene itself may control ER expression. These epigenetic changes can play an important role in the loss of hormone dependence in breast cancer.