Gene in Brain Also Expressed in Metastatic Breast Cancer

Gene in Brain Also Expressed in Metastatic Breast Cancer

February 17, 2016

Researchers have discovered that a gene in the brain is also expressed in metastatic breast cancer. The team from The Wistar Institute-that specializes in cancer research and vaccine development-also observed how a version of the gene with edited RNA prevents metastasis.

Researchers have discovered that a gene in the brain is also expressed in metastatic breast cancer. The team from The Wistar Institute-that specializes in cancer research and vaccine development-also observed how a version of the gene with edited RNA prevents metastasis. The findings were first published online by the journal Nature Communications.

The team analyzed The Cancer Genome Atlas (TCGA) breast cancer data and identified 41 genes whose expression is inversely correlated with survival. GABAA receptor alpha3 (Gabra3), usually only expressed in the adult brain, is also expressed in breast cancer. High expression of Gabra3 is inversely correlated with breast cancer survival.

Learning which genes that may cause tumor cells to metastasize is very important to further the understanding of the breast cancer lifecycle. If caught early, and before it has spread to other areas, chances of survival are greater. If the cancer is located only in the breast, the 5-year relative survival rate of patients with breast cancer is 99%. If the cancer has spread to the regional lymph nodes, the 5-year survival rate is 85%. If the cancer has spread to a distant part of the body, the 5-year survival rate is 25%.

Gabra3 promotes tumor growth by activating the AKT pathway, which in turn causes breast cancer cell migration, invasion, and metastasis.  Gabra3 is highly expressed in cancer tissues, but not in healthy breast tissues. Additionally, because it's a cell surface molecule it could be a potential drug target.

Certain types of Gabra3 are actually able to suppress breast cancer metastasis. Gabra3 that has undergone RNA editing was found only in noninvasive breast cancers. When RNA is edited, a breast cancer with this specific type of Gabra3 was unable to spread to other organs.

“We believe this is the first time that anyone has demonstrated the importance of RNA editing in breast cancer,” said Qihong Huang, MD, PhD, in a press release. “A combination strategy that that involves targeting Gabra3 while also upregulating the expression of RNA editing molecules could be an effective strategy for managing metastatic breast cancer.”

Wistar will continue to study the role of Gabra3 in breast cancer metastasis and is seeking collaborative partners to develop blood-brain barrier impermeable GABAA receptor antagonists as next generation oncology therapeutics.