Identification of breast tumor suppressor may help assess patient prognosis
A new study identifies the Proline-Rich Homeodomain protein (PRH/HHEX) as a tumor suppressor in breast cancer.
Published in the journal Oncogenesis, a study conducted by scientists at the University of Birmingham and University of Bristol shows that PRH plays a tumor suppressive role in the breast. This finding explains the phenomenon that low PRH mRNA levels correlate with poor outcome in breast cancer patients.
PRH is a transcription factor that regulates gene expression. It acts as a promoter in some instance and an inhibitor in other instances. There is evidence that PRH displays both tumor suppressor and oncogenic activity in different types of cancer. But its role in breast cancer remains unclear.
To address this question, P-S Jayaraman, a researcher at the Institute of Cancer and Genome Biology, University of Birmingham, and colleagues examined PRH expression in breast samples from healthy people and patients with primary breast tumors. They did this by using a common analytical method called immunohistochemistry (IHC). IHC results showed that nuclear localization of the PRH protein is decreased in primary breast tumors in comparison with normal breast.
Next, the researchers investigated the effect of PRH overexpression in human breast adenocarcinoma MCF-7 cells, and found that PRH overexpression resulted in a remarkable decrease in the number of cancer cells as well as an increase in apoptosis. By contrast, when PRH is reduced, the formation of cancer stem cell-like cells was dramatically increased.
The researchers also found PRH regulates the expression of genes associated with proliferation, angiogenesis, and cancer stem cells. Knockdown of PRH causes additional tumorigenic properties.
These findings are in agreement with their observation that breast cancer patients with low expression of PRH mRNA tend to have a poorer relapse-free survival compared with those with high PRH.
In conclusion, the data support PRH as a breast tumor suppressor. Therefore, monitoring the levels and activity of PRH protein may help access the prognosis of patients with breast tumors.
