Alternative splicing and the progesterone receptor in breast cancer.
Alternative splicing and the progesterone receptor in breast cancer.
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DOI：
10.1186/bcr2097
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Tyson-Capper AJ
中科院分区：
文献类型：
--
作者：
Cork DM;Lennard TW;Tyson-Capper AJ
孕激素受体状态是乳腺癌激素反应性和疾病预后的标志。孕激素受体阴性的肿瘤通常比孕激素受体阳性的肿瘤预后更差。观察到的孕激素受体丢失可能是通过一系列机制，包括产生目前的筛查方法无法检测到的选择性剪接的孕激素受体变体。许多孕激素受体mRNA变异体被描述为缺失了编码不同蛋白质功能结构域的各种完整、多个或部分外显子。这些变异可能会改变组织的孕激素反应，并导致与乳腺癌相关的异常生长。这些剪接变异体缺乏特定的功能结构域，也可能使它们无法被检测到，或者无法通过常规抗体与全长孕酮受体区分开来。全面研究孕激素受体剪接变异体在乳腺癌中的表达谱和活性是促进我们对肿瘤激素受体状态的理解所必需的。这反过来可能有助于开发新的疾病预后生物标志物，并改善辅助治疗决策。
Progesterone receptor status is a marker for hormone responsiveness and disease prognosis in breast cancer. Progesterone receptor negative tumours have generally been shown to have a poorer prognosis than progesterone receptor positive tumours. The observed loss of progesterone receptor could be through a range of mechanisms, including the generation of alternatively spliced progesterone receptor variants that are not detectable by current screening methods. Many progesterone receptor mRNA variants have been described with deletions of various whole, multiple or partial exons that encode differing protein functional domains. These variants may alter the progestin responsiveness of a tissue and contribute to the abnormal growth associated with breast cancer. Absence of specific functional domains from these spliced variants may also make them undetectable or indistinguishable from full length progesterone receptor by conventional antibodies. A comprehensive investigation into the expression profile and activity of progesterone receptor spliced variants in breast cancer is required to advance our understanding of tumour hormone receptor status. This, in turn, may aid the development of new biomarkers of disease prognosis and improve adjuvant treatment decisions.
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