Harvard Medical School's scientists have recently discovered something totally unexpected about ER (estrogen receptor) positive breast cancer through a study they jointly conducted with other research center colleagues around the country. In a range of lab experiments, they also learned that SLC7A5, the cell surface protein helping cells to obtain leucine, has an impact on the ER positive breast cancer cells' response to tamoxifen.
The paper was published in the scientific journal Nature. The authors of the study took note of the fact that this SLC7A5 is a necessary element in causing the body to resist treatment by tamoxifen. They inferred that this protein might be designated as a possible target to overcome resistance to the tamoxifen drug in treating ER positive types of breast cancer.
This is an important discovery because in nearly 75 percent of breast cancer cases, the estrogen hormone enables the malignant tumors to both develop and spread. The reason is that the cancer cells (much like normal breast cells) possess estrogen receptors which permit them to get estrogen hormone-driven growth signals.
Roughly one-eighth of American women will suffer from breast cancer at some point in their lives. In the overwhelming majority of cases, the cancer requires this estrogen hormone to both develop and expand. Tamoxifen is the treatment drug of choice in many cases of Estrogen receptor positive breast cancer tumors. Tamoxifen actually blocks out the impact of estrogen hormones on these tumors. The problem arises when a high number of tumors finally gain resistance to tamoxifen. This permits dormant cancer to metastasize or recur.
Thanks to another discovery at the Beth Israel Deaconess Medical Center's Cancer Center, researchers have uncovered an unanticipated correlation between amino acid leucine levels and the increase of tamoxifen resistance in the tumors of ER breast cancer. The researchers were headed by Dr. Senthil Muthuswamy, PhD. They found a critical protein that imports this leucine into the cells and controls the tamoxifen sensitivity in ER cells within a laboratory setting. Also published in the journal Nature, these two related discoveries unveil a possible revolutionary strategy in overpowering resistance to the endocrine drugs used for ER breast cancer sufferers.
Muthuswamy explained in the journal that these patients whose ER breast cancers become endocrine resistant will likely see their cancer metastasize and then have a very low life expectancy of under five years total to survive. This is because their options for treatment are limited without endocrine drugs. He stated that their findings mean that by reducing the levels of leucine, they can reduce the tumor cell proliferation while boosting leucine levels expands it. The discovery also signifies that a lower leucine diet can dramatically help patients suffering from ER breast cancer to survive and successfully respond to the critical treatment.
About Leucine the Amino Acid
Leucine proves to be an amino acid, of which there are 20. They are critical as the protein building blocks of the human body. Leucine is one of nine crucial amino acids that your body must get from food. It is found in rich amounts in foods such as fish, pork, chicken, and beef. The body's cells are not able to produce leucine by themselves.
This research allowed the researchers to test out decreasing leucine levels in their dish cultured cells to impact the growth rates of ER breast cancer cells. Their report showed that by decreasing the levels of leucine, they suppressed the division of the ER breast cancer cells. Providing a ten times increase in the amount of leucine to the ER breast cells caused it to expand.
The research further suggested that patients might benefit by consuming plant proteins as opposed to animal proteins, as the animal ones have larger quantities of leucine. It means that a diet strategy can assist victims of ER breast cancer. By reducing their leucine levels, this can make their ER breast cancer case more manageable and treatable.
One surprise in the research for the scientists was that cells which had already been induced to tamoxifen resistance obtained the capability of growing even with lower leucine levels. An additional investigation uncovered the connection with the cell surface protein SLC7A5 that is necessary for leucine to make it into the cells. This exists in greater amounts in those cells that have become resistant to tamoxifen. Because of this, lead researcher Muthuswamy concludes that by inhibiting the SLC7A5, they may potentially better treat the ER breast cancer cases.
This research opened the door to understanding the connection with estrogen biology and intracellular leucine levels of cells. The scientists now have a brand new study of estrogen receptor biology that will enable them to come up with newer and better strategies for helping out victims of estrogen receptor breast cancers.
This discovery agrees with prior reports claiming that by diminishing the amount of leucine intake, it can result in superior metabolic health. It was already known that by reducing the total quantities of proteins in your diet, this would boost longevity and all around metabolic health (in studies conducted on rodents). Recently performed studies in humans, as well as mice, revealed that lower leucine diets can offer similar advantages. The downside is that restricting proteins makes it more difficult to attain a person's requirements for daily nutrients. Yet diets comprised primarily of lower leucine containing plant proteins could be the superior choice for those women who are suffering from Estrogen Receptor breast cancer.
A follow up is already underway for the Harvard led teams. Dr. Muthuswamy's group is studying to learn if a diet that is leucine restricted can inhibit growth or improve the therapy response for those ER breast cancer cells found in mice.
