It is a well established fact that any genetic alterations in either the BRCA1 or BRCA2 gene can predispose to breast cancer. The BRCA1 gene, has been known to play a significant role// in the utilization of estrogen in cells present in the breast. Researchers from Georgetown University Medical Center have now found that the BRCA1 gene also controls the activity of another important sex hormone, progesterone.
The results of the present study can be found in the latest issue of Molecular Endocrinology. This finding could eventually serve to explain the increased susceptibility of women with BRCA1 mutations to suffer form different forms of hormone dependent cancer, such as those of the cervix, endometrium and breast.
The researchers were interested in finding out how loss of BRCA1 activity could predispose to formation of hormone dependent tumors. Progesterone was taken up as the main target, as women who used hormone replacement therapy (HRT ) were found to have an increased cancer susceptibility than those on estrogen alone.
The utilization of progesterone is highly regulated. Furthermore, the activation occurs when there is a necessity for cell growth, such as during the menstrual cycle and during pregnancy. Specific receptor molecules, located inside the cell play a critical role in the binding and transport of progesterone. A gene expression is then manifested due to activation of the receptor.
In order to understand the role played by BRCA1 in signal transduction of the progesterone receptor, the researchers used breast cancer cell lines, sensitive to progesterone levels. These cell lines were genetically manipulated to either under express or over express the BRCA1 gene. Breast tissue, in which BRCA1 was partially deleted was also used for the study. The cell lines were treated with varying concentrations of estrogen, progesterone and estrogen-progesterone combination.
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