Breast cancer is one of the most common malignant tumors in women. Previous studies have shown that estrogen is an important cytokinesis agent for breast cancer, which is mediated by estrogen receptor ER in breast tissue. ER positive has become the basis for anti-estrogen therapy in breast cancer patients.
Other studies have shown that the activation level of the ribosomal protein S6 kinase A (RSK) is positively correlated with the response to estrogen therapy in breast cancer patients, but the molecular mechanism remains unclear.
In a recent study published in the international journal Cancer Research, researchers from Vanderbilt University, USA, using in vitro and in vivo models of multiple ER+ breast cancers, found that ER traps activated RSK2 in the nucleus to promote malignant transformation of cells, facilitating the growth of metastatic tumors.
This study shows that RSK2 activates a transcriptional regulatory network promoting malignant transformation through its N-terminal interaction with ER, which is important for ER+ cells in the breast. This discovery provides a gene expression signature that can help grade a patient’s tumor based on ER level.
The results also showed that ER+ tumor growth was strongly dependent on RSK2 in the nucleus, and transgenic mice with stable expression of RSK2 in the nucleus in breast cells would develop high-grade ductal adenocarcinoma in situ.
Breast cells isolated from the transgenic mouse model and implanted elsewhere in the body can spread and establish metastases.
Anti-estrogen drugs can disrupt the interaction between RSK2 and ER, promoting RSK2 entry into the cytoplasm and affecting tumor formation.
These results suggest that RSK2 is an important participant in ER mediated transcriptional regulation, and this study provides insights into ER+ breast cancer grading and provides a mechanistic explanation for how antiestrogen therapy works.