Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China; Company Ten of Cadet Brigade, Third Military Medical University, Chongqing 400038, China.
J Steroid Biochem Mol Biol. 2013 Nov;138:17-23. doi: 10.1016/j.jsbmb.2013.02.010. Epub 2013 Mar 6.
Breast cancer is the leading cause of cancer death for women worldwide. Various therapeutic approaches have been proposed, among which endocrine therapy has recently become popular due to the high sensitivity of breast tissues to steroids such as estrogens and progesterone. The underlying mechanisms of steroid regulation in breast cancer cell proliferation, invasiveness, metastasis and endocrine resistance, however, remain largely unknown. Steroid receptor coactivator-1 (SRC-1) has attracted much attention because it is an important co-regulator and plays a pivotal role in modulating the transcriptional activities of steroid nuclear receptors. Accumulated research has established a strong correlation between SRC-1 and the pathological progression or disease-related features of breast cancer, which supports its potential as a target for specific therapeutic intervention in the clinical management of breast cancer. In addition, a diverse group of downstream molecules have also been shown to participate in various functional pathways related to SRC-1-associated regulation of breast cancer. These downstream molecules are also considered promising therapeutic targets, providing additional options for targeted treatments. In this review, the expression of SRC-1 in breast cancer and the close relationships between SRC-1 and the cell proliferation, invasiveness, metastasis and endocrine resistance of breast cancer will be discussed, followed by a brief summary of its putative functional mechanisms with an emphasis on the potential therapeutic role of SRC-1.
乳腺癌是全球女性癌症死亡的主要原因。已经提出了各种治疗方法，其中内分泌治疗由于乳房组织对雌激素和孕激素等类固醇的高度敏感性而最近变得流行。然而，类固醇调节在乳腺癌细胞增殖、侵袭、转移和内分泌抵抗中的潜在机制在很大程度上仍然未知。类固醇受体共激活因子-1（SRC-1）引起了广泛关注，因为它是一种重要的共调节剂，在调节类固醇核受体的转录活性方面起着关键作用。积累的研究已经建立了 SRC-1 与乳腺癌的病理进展或疾病相关特征之间的强烈相关性，这支持了其作为乳腺癌临床管理中特定治疗干预的潜在目标。此外，还发现了一组不同的下游分子参与与 SRC-1 相关的乳腺癌调节相关的各种功能途径。这些下游分子也被认为是有前途的治疗靶点，为靶向治疗提供了更多选择。在这篇综述中，将讨论 SRC-1 在乳腺癌中的表达以及 SRC-1 与乳腺癌细胞增殖、侵袭、转移和内分泌抵抗之间的密切关系，并简要总结其假定的功能机制，重点介绍 SRC-1 的潜在治疗作用。
