Gene Uncovered Associated with Aggressive Breast Cancer

TNBC is characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), and represents the most aggressive subtype of breast cancer, with a high rate of relapse and no available therapeutic targets.

Scientists at the A*STAR Genome Institute (Singapore) used quantitative polymerase chain reaction (qPCR) and western blotting for micro ribonucleic acid (miRNA) profiling of breast cancer cells and quantitative real-time PCR for validation. Total RNAs were isolated and purified with the miRNeasy Mini Kit (Qiagen; Venlo, The Netherlands). The miRNA expression array hybridization was performed using the Human miRNA Microarray Kit V3 (Agilent, Santa Clara, CA, USA), and data analysis was performed. Immunohistochemistry was also implemented.

The team found that small RNA, often called microRNA, is lost in highly metastatic TNBC cells but not in luminal breast cancer. As a result, the gene RAS Protein Activator Like 2 (RASAL2), which is negatively regulated by this microRNA, is upregulated in a set of TNBC tumors. The study showed that TNBC patients whose tumors have high expression of RASAL2 tend to have a lower survival rate as compared to patients whose tumors have low levels of this gene. Additionally, the study showed that genetic knockdown of RASAL2 gene can lead to reduced metastasis in breast cancer mouse model.

Qiang Yu, PhD, a professor and project leader of the study, said, “Cancer is an extremely heterogeneous disease, where many molecular processes have gone wrong in their own ways. Rather than a tumor suppressor, we show here that RASAL2 actually acts as a cancer promoting molecule in TNBC. This reminds us that the same molecule can function very differently in different subtypes of cancers, a phenomenon which has often been seen before.” The study was published on November 10, 2014, in the Journal of Clinical Investigation.

Related Links:
A*STAR Genome Institute
Qiagen 
Agilent