Researchers at the Cancer Center at Beth Israel Deaconess Medical Center revealed an unexpected relationship between levels of the amino acid leucine and the growth of tamoxifen resistance in estrogen-receptor positive breast cancer
About one in eight women in the United States will develop breast cancer in her lifetime. The vast majority of these cancers rely on the hormone estrogen to grow. Estrogen-receptor positive (ER+) breast cancer tumors are frequently treated with the drug tamoxifen, which blocks the hormone’s effect on the tumor. However, many tumors eventually become resistant to tamoxifen, allowing cancer to recur or metastasize.
Now, a team of researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) has discovered an unexpected relationship between levels of the amino acid leucine and the development of tamoxifen resistance in ER+ breast cancer. Led by Senthil K. Muthuswamy, PhD, the researchers further identified a key protein that imports leucine into cells and modulates sensitivity to tamoxifen in ER+ cells in the lab setting. The findings, published today in the journal Nature, reveal a potential new strategy for overcoming resistance to endocrine drugs in ER+ breast cancer patients.
“Patients with ER+ breast cancer who develop endocrine-resistant and metastatic cancer have very poor life expectancy, usually less than five years survival, because they have limited treatment options available,” said Muthuswamy, who is Director of the Cell Biology Program and Deputy Director of Translational Research in the Cancer Research Institute at BIDMC. “Our findings in the lab demonstrate that decreasing leucine levels suppresses proliferation of tumor cells, whereas increasing leucine enhances it. Furthermore, the findings open up the possibility that a low-leucine diet could be beneficial for patients with ER+ breast cancer.”
Leucine is one of the 20 amino acids – the building blocks of all proteins in our body – and is among the 9 essential amino acids that must be obtained via food. Beef, chicken, pork and fish are all rich sources of leucine. Because cells can’t produce leucine on their own, Muthuswamy and colleagues were able to test how manipulating levels of leucine in cells cultured in a dish would affect the growth of human derived ER+ breast cancer cells. The researchers reported that decreasing leucine levels suppressed ER+ breast cancer cells’ division, while a tenfold increase of the amino acid enhanced it.
|Read on: Diet High in Leucine May Fuel Breast Cancer’s Drug Resistance|