MiRNA-21's role in Herceptin resistanceThe hypothesis was tested in three HER2-overexpressing breast cancer cell lines. In a series of experiments, miRNA-21 and/or a control miRNA were introduced and expressed in the HER2-overexpressing cell lines. The cells were then treated with Herceptin. The researchers found that cells with higher levels of miRNA-21 had reduced PTEN expression and were significantly more resistant to the drug than were the control cells.

The researchers also determined that miRNA-21 reduces PTEN expression by inhibiting PTEN messenger RNA at a specific site in the PTEN transcript in breast cancer cells.

In another experiment, when the researchers downregulated miRNA-21 in high HER2-expressing cells, cellular PTEN levels rose, and the cells became more sensitive to Herceptin compared to control miRNA cells.

The researchers then sought to determine the clinical relevance of their findings by measuring levels of miRNA-21 in tumor samples from patients with HER2-positive breast cancer treated with Herceptin. They found a significant correlation between high levels of miRNA-21 and poor patient response to Herceptin, as well as a correlation between elevated miRNA-21 and disease progression.

Rehman also observed that patients with low tumor levels of miRNA-21 tend to experience either a partial response to Herceptin or stable disease.

SOURCE The University of Texas M. D. Anderson Cancer Center