The Center for Genomic Regulation discovers mechanism connecting progesterone and hereditary breast cancer

BY BIOCAT

It has long been known that the existence of mutations in the BRCA1 gene can cause breast cancer in approximately 80% of cases, as well as ovarian cancer in 54% of cases. Although this gene is related to other types of cancer, the fact that it is so specific to breast cancer has sparked great interest in the scientific and medical community.

One of the most accepted hypotheses to explain the specificity of BRCA1 in the development of cancer in tissues with high levels of female hormones is the role this gene plays in regulating the activity of these hormones.

In a paper published in the journal Cancer Research, researchers from the Barcelona Center for Genomic Regulation (CRG), Miguel Beato and Veronica Calvo, describe the role BRCA1 plays in relation to one of the two female hormones: progesterone. Their work demonstrates that BRCA1 plays a crucial role in controlling progesterone receptors found in cells.

“When the BRCA1 gene is mutated and is not expressed correctly, the cell has more progesterone receptors consequently increasing the effect on cell proliferation," explains Miguel Beato who is responsible for the work and the director of the CRG. "We knew that this gene played an important role in breast cancer but now we know what one of the mechanisms used is" adds Beato.

BRCA1 acts on two levels: firstly, on the amount of progesterone receptor found in cells and, secondly, by controlling the expression of progesterone genes.

These findings demonstrate the direct relationship between an excess of the cellular effects of progesterone and the risk of developing breast cancer. Knowledge of the mechanism through which the BRCA1 gene acts allows us to understand its importance in the development of breast cancer and helps in designing improved therapies, which act directly on the molecules involved.

Furthermore, the work of Veronica Calvo and Miguel Beato may influence cancer prevention. Just as hormonal contraceptive methods were modified when the direct relationship between estrogen levels and the risk of developing breast cancer was demonstrated, perhaps the contribution of these researchers on the role of progesterone will also have repercussions on the prescription of contraceptive treatment.

Reference work: Verónica Calvo and Miguel Beato. BRCA1 Counteracts Progesterone Action by Ubiquitination Leading to Progesterone Receptor Degradation and Epigenetic Silencing of Target Promoters. Published in Cancer Research (2011), doi: 10.1158/0008-5472.CAN-10-3670.