MED1 and Associated Diseases
As a leader in the field of gene therapy, the core expertise of Creative Biolabs covers central nervous system diseases, pain, inflammation and immunology, fibrosis, metabolic diseases, oncology and anti-infection and other therapeutic areas, and extends to many rare diseases. With rich experience and cutting-edge technology platforms, Creative Biolabs is committed to providing cost-effective gene therapy services to global customers to meet your unique needs. We are willing to share our background knowledge related to gene therapy, here we provide a brief introduction to the mediator complex subunit 1 (MED1) gene.
Introduction of MED1
MED1 is a protein-coding gene that encodes a subunit of the evolutionarily highly conserved multiprotein mediator complex. MED1 is involved in multiple pathways and plays different roles in them. The protein encoded by this gene is a subunit of the cofactor necessary for the specificity protein 1 (Sp1) activation complex, which plays a crucial role in the activation of SP1. In addition, this protein serves as a component of other multisubunit complexes, such as thyroid hormone receptors (TR) -associated protein, which facilitates TR function on DNA templates. It also regulates p53-dependent apoptosis and is required for adipogenesis.
Fig.1 Alternative pathways for Mediator recruitment to NR target genes. (Chen, 2011)
Role of MED1 in Human Cancer
Based on the biochemical activities of its products, MED1 was identified as a candidate tumor suppressor gene. Indeed, frameshift mutations in the MED1 gene have been reported in a variety of human cancers, including gastric, colorectal, and pancreatic cancers. The relationship between MED1 and breast cancer has been studied extensively. MED1 protein is known to be overexpressed in more than 50% of breast cancers. In addition, the MED1 gene is co-amplified with human epidermal growth factor receptor 2 (HER2), another important breast cancer gene receptor. Clinically, the expression level of MED1 protein is closely related to the disease-free survival rate of breast cancer patients, and it is worth noting that recent studies have shown that the frequency of MED1 mutations in circulating tumor cells of patients after treatment increases. Thus, MED1 is established as a key regulator involved in the process of breast cancer tumorigenesis.
Fig.2 MED1 in human breast cancer. (Leonard, 2019)
Related Mechanisms in Breast Cancers
As mentioned above, MED1 overexpression is found in approximately half of the breast cancers. Notably, the MED1 gene is located in a genomic region containing HER2, the HER2 amplicon, which was co-amplified with HER2 in almost all cases. The results of human breast cancer tissue microarray analysis further confirmed that MED1 protein levels are highly correlated with the HER2 status of breast cancer. Importantly, MED1 is coamplified with HER2 and activated by the HER2 signaling cascade. MED1 is also inextricably linked to HER2-mediated tumorigenesis and the response to anti-HER2 therapy. Therefore, MED1 represents a novel crosstalk point in the HER2 pathway and may serve as an attractive therapeutic target for the treatment of breast cancer.
Combining state-of-the-art technology in the field of gene therapy with expertise in relevant target classes, our one-stop shop has repeatedly proven to be the driving force for the success of many projects. If you are interested in our gene therapy services, please contact us in time for more details.
References
- Chen, W.; Roeder, R.G. Mediator-dependent nuclear receptor function. In Seminars in cell & developmental biology. 2011, 22(7): 749-758.
- Leonard, M.; Zhang, X. Estrogen receptor coactivator mediator subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer. Journal of Zhejiang University-SCIENCE B. 2019, 20(5): 381-390.
