Abstract 4703: Role of REST in the regulation of MMP24 and estrogen sensitivity in breast cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.4703-4703
• Main Authors: Vargheese, Aditya M., Cloud, Ashley, Gunewardena, Sumedha, Shimak, Raeann, Kumaraswamy, Easwari, Jensen, Roy A., Chennathukuzhi, Vargheese M.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2020-4703

Breast cancer, the most common malignancy in women, is very difficult to detect and treat due to its heterogeneity. An important subset of breast cancers, Luminal or ER/PR positive tumors, lack REST (repressor element 1 silencing transcription factor) protein but not its mRNA. REST is a tumor suppressor and is known to play a role in regulating neurodegenerative diseases such as Alzheimer's. The loss of REST leads to the dysregulation of its target genes, many of which are involved in tumorigenesis. About 20% of breast cancers show loss of REST expression, yet little to nothing is currently known about the role REST plays in tumor growth. We hypothesized that the loss of REST promotes breast cancer growth by altering cell signaling. Our results show that knockdown of REST in MCF7 cells (ER/PR positive) causes similar gene dysregulation as seen in aggressive forms of breast cancers. Also, Ingenuity Pathway Analysis (IPA®) of our RNA sequencing results showed that REST knockdown leads to significant increase in estrogen receptor signaling in MCF7 cells. Upregulation of estrogen receptor expression has been associated with tumor progression. In addition, REST knockdown led to significant increases in the expression of MMP24 (>20-fold, p