Rayala Suresh K, den Hollander Petra, Balasenthil Seetharaman, Yang Zhibo, Broaddus Russell R, Kumar Rakesh
Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
EMBO Rep. 2005 Jun;6(6):538-44. doi: 10.1038/sj.embor.7400417.
Overexpression and phosphorylation of dynein light chain 1 (DLC1) have been shown to promote the growth of breast cancer cells. However, the role of DLC1 in the action of the oestrogen receptor (ER) remains unknown. Here, we found that oestrogen induces the transcription and expression of DLC1. DLC1 facilitated oestrogen-induced ER transactivation and anchorage-independent growth of breast cancer cells. We show that DLC1 interacts with ER, and such interaction is required for the transactivation-promoting activity of DLC1. Further, DLC1 expression led to enhanced recruitment of the DLC1-ER complex to the ER-target gene chromatin. Conversely, DLC1 downregulation compromised the ER-transactivation activity and also its nuclear accumulation, suggesting a potential chaperone-like activity of DLC1 in the nuclear translocation of ER. Together, these data define an unexpected upregulation of DLC1 by oestrogen and a previously unrecognized DLC1-ER interaction in supporting and amplifying ER-initiated cellular responses in breast cancer cells.
动力蛋白轻链1（DLC1）的过表达和磷酸化已被证明可促进乳腺癌细胞的生长。然而，DLC1在雌激素受体（ER）作用中的角色仍不清楚。在此，我们发现雌激素可诱导DLC1的转录和表达。DLC1促进雌激素诱导的ER反式激活以及乳腺癌细胞的非锚定依赖性生长。我们表明DLC1与ER相互作用，且这种相互作用是DLC1促进反式激活活性所必需的。此外，DLC1的表达导致DLC1-ER复合物向ER靶基因染色质的募集增强。相反，DLC1的下调损害了ER反式激活活性及其核积累，表明DLC1在ER核转位中具有潜在的伴侣样活性。总之，这些数据确定了雌激素对DLC1的意外上调以及在支持和放大ER启动的乳腺癌细胞中的细胞反应方面以前未被认识的DLC1-ER相互作用。
