The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer.
The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer.
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DOI：
10.1007/s10549-009-0405-2
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发表时间：
2009-07
影响因子：
3.8
通讯作者：
Riegel, Anna T.
中科院分区：
文献类型：
--
作者：
Lahusen, Tyler;Henke, Ralf T.;Kagan, Benjamin L.;Wellstein, Anton;Riegel, Anna T.
AIB 1（在乳腺癌中扩增1），也称为SRC-3和NCoA-3，是p160核受体辅激活因子家族的成员，被认为是乳腺癌中的重要癌基因。人类乳腺癌中AIB 1水平的升高与临床预后不良相关。AIB 1与表皮生长因子受体（EGF/HER）酪氨酸激酶家族成员（如HER 2）的过度表达与他莫昔芬治疗耐药和无病生存期降低相关。在细胞培养和啮齿动物中的许多功能研究表明，AIB 1在乳腺癌中具有多效性作用。最初，AIB 1被证明在乳腺上皮细胞的雌激素依赖性增殖中起作用。然而，AIB 1也影响非依赖性乳腺癌的生长，并且AIB 1水平限制乳腺癌细胞中IGF-1、EGF和调蛋白刺激的生物反应，因此PI 3 K/Akt/mTOR和其他EGFR/HER 2信号传导途径受AIB 1蛋白水平变化的控制。AIB 1的细胞水平和活性反过来在转录、mRNA稳定性、翻译后修饰水平以及通过蛋白质半衰期的复杂控制来调节。特别地，AIB 1活性及其半衰期通过许多翻译后修饰来调节，包括通过作为多种信号转导途径的组分的激酶进行的丝氨酸、苏氨酸和酪氨酸磷酸化。本文综述了AIB 1在多个水平的失调如何导致乳腺癌的发生和进展的可能机制，以及其作为乳腺癌治疗反应的预测因子和可能的治疗靶点的作用。
AIB1 (amplified in breast cancer 1), also called SRC-3 and NCoA-3, is a member of the p160 nuclear receptor co-activator family and is considered an important oncogene in breast cancer. Increased AIB1 levels in human breast cancer have been correlated with poor clinical prognosis. Overexpression of AIB1 in conjunction with members of the epidermal growth factor receptor (EGF/HER) tyrosine kinase family, such as HER2, is associated with resistance to tamoxifen therapy and decreased disease-free survival. A number of functional studies in cell culture and in rodents indicate that AIB1 has a pleiotropic role in breast cancer. Initially AIB1 was shown to have a role in the estrogen-dependent proliferation of breast epithelial cells. However, AIB1 also affects the growth of hormone-independent breast cancer and AIB1 levels are limiting for IGF-1-, EGF- and heregulin-stimulated biological responses in breast cancer cells and consequently the PI3 K/Akt/mTOR and other EGFR/HER2 signaling pathways are controlled by changes in AIB1 protein levels. The cellular levels and activity of AIB1 are in turn regulated at the levels of transcription, mRNA stability, post-translational modification, and by a complex control of protein half life. In particular, AIB1 activity as well as its half-life is modulated through a number of post-translational modifications including serine, threonine and tyrosine phosphorylation via kinases that are components of multiple signal transduction pathways. This review summarizes the possible mechanisms of how dysregulation of AIB1 at multiple levels can lead to the initiation and progression of breast cancer as well as its role as a predictor of response to breast cancer therapy, and as a possible therapeutic target.
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影响因子：
3.4
作者：
Fleming, FJ;Myers, E;Young, LS
通讯作者：
Young, LS
DOI：
10.1073/pnas.0403621101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Biswas, DK;Shi, Q;Iglehart, JD
通讯作者：
Iglehart, JD
影响因子：
5.3
作者：
Hossain, Anwar;Kuo, Macus T.;Saunders, Grady F.
通讯作者：
Saunders, Grady F.
影响因子：
8
作者：
Farmer, P;Bonnefoi, H;Iggo, R
通讯作者：
Iggo, R
影响因子：
3.8
作者：
Dihge, Looket;Bendahl, Par-Ola;Ferno, Marten
通讯作者：
Ferno, Marten