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首页> 美国政府科技报告 >Integrin-dependent Antagonism of Tamoxifen Therapy through Transcriptional Replacement: Establishing a Basis for a New Combined Therapy
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Integrin-dependent Antagonism of Tamoxifen Therapy through Transcriptional Replacement: Establishing a Basis for a New Combined Therapy

机译：通过转录替代治疗对他莫昔芬治疗的整合素依赖性拮抗作用：为新的联合治疗奠定基础

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Accruing evidence suggests that integrin-dependent cell attachment signaling, and estrogen hormonal response are closely interconnected. For example, studies by us and others of the BCAR proteins (BCAR1 and BCAR3: (1, 2)) have indicated that these proteins physically associate with each other, and function both in signal transduction relevant to integrin stimulation, and in mediation of Tamoxifen (Tam) resistance. The goal of this proposal was to explore the interrelationship between integrin signaling, cell attachment status, and Tam resistance. A specific hypothesis was that activation of integrin signaling reduces the Tam-dependent inhibition of essential estrogen- dependent transcription. In particular, the proposal sought to explore how the formation of organized three-dimensional structures (spheroids) by metastasizing tumor cells, which greatly enhances their resistance to treatment with a number of drugs reviewed in (4), might modulate Tam resistance and the estrogen-dependent transcriptional program. As described below, we found that spheroids unexpectedly did not result in increased Tam resistance. However, we did find that manipulation of expression of BCAR1 resulted in changes in the transcription of estrogen-regulated genes, suggesting the initial hypothesis of an integrin-estrogen connection at the level of transcription is worth further investigation.

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