The female hormone progesterone actually has a life-enhancing effect: it stimulates the build-up of the lining of the uterus so that a fertilized egg cell can nest there and grow into a child. But alas, it works hand in hand with a defective gene - then the hormone can suddenly cause damage.
A sad result: Breast cancer is the most common type of cancer and the fifth most common cause of death in German women. More than 55,000 people in Germany are diagnosed with this type of cancer every year. In addition to a number of other factors, prolonged hormone treatment with estrogens and progestins during menopause promotes the development of breast cancer, and changes in the BRCA1 gene increase the risk of breast cancer in some women.
As a tumor suppressor, this gene is supposed to prevent the development of cancer by repairing damage to the DNA. However, if it has been degenerated by a mutation, it can no longer fulfill this task and the risk of cancer increases - but only for breast and ovarian cancer. And this despite the fact that the defective gene is active throughout the body. So why does such a genetic defect only increase the risk of these two types of cancer?
Aleksandra Poole's team led by Eva Lee from the University of California in Irvine investigated this question. The scientists suspected that the interaction of BRCA1 and progesterone receptors could play a crucial role. This is because BRCA1 suppresses breast cancer by interacting with progesterone-binding sites, the progesterone receptors, and women treated with progesterone also have an increased risk of breast cancer.
In order to further decipher the connection between BRCA1, progesterone and breast cancer, scientists worked with genetically modified mice which, in addition to the BRCA1 gene, also lack p53 – another tumor suppressor. This gene could jump into the breach as another guardian in the event of BRCA1 failure and try to suppress the development of cancer. These rodents are therefore particularly susceptible to cancer.
The scientists observed that the epithelial cells of the mammary glands of these animals multiplied at an unusual rate. In addition, these cells formed an exceptionally large number of receptors for progesterone. This local accumulation could explain the site-specific carcinogenic effect of the defective gene.
Now the researchers administered mifepristone, a substance that blocks the receptors for progesterone and thus switches off its effect, to some of the rodents. That's why it - also known as RU486 - is used for abortion in unwanted pregnancies, because it prevents the progesterone-promoted build-up of the uterine lining.
Progesterone plays a role in the development of cancer by promoting the proliferation of breast gland cells that carry a breast cancer gene. Mifepristone can block this mechanism
(Eva Lee) The untreated animals developed palpable tumors within a few months – the mice treated with the progestin blocker, on the other hand, remained cancer-free. So there is a clear connection between mutated BRCA1 and progesterone.
From their observations, the working group concludes that progesterone promotes the development of breast cancer in cooperation with a defective BRCA1 gene. Conversely, substances such as mifepristone, which paralyze the effects of progesterone, could possibly provide preventive protection for the high-risk group of women with a mutated BRCA1 gene.