The research could help develop better therapies for the new subtype of adenocarcinoma patients -
Lung cancer is the most common cause of cancer death this represents about a third of all deaths related to the tumor. Adenocarcinoma, a cancer non-small cell lung (NSCLC) represent approximately 40 percent of cancer diagnoses, but few treatments are available for the disease.
A team of researchers led by Elena Levantini, PhD, a research associate in hematology-oncology at Beth Israel Deaconess Medical Center (BIDMC), medical instructor at Harvard Medical School and member of the Institute of cells Harvard strains identified a subtype of human adenocarcinoma. The research could help determine who is most at risk of developing lung tumors that can lend itself to a new therapy to inhibit their progress. The results - in collaboration with the Institute of Cancer Sciences at the National University of Singapore (NUS CSI) - were published today in the journal Science Translational Medicine
"Advances in treatment lung cancer require a better understanding of. molecular origins of this deadly disease, "said corresponding author last Levantini, who is also a researcher at the Institute of biomedical technologies of the National research Council (CNR-ITB). "Understanding the differences between lung cancers could also lead to innovations in treatment strategies and allow us to overcome drug resistance, relapse and progression of the disease."
Levantini and colleagues previously showed that NSCLC tumor cells often express too little or none of a transcription factor called C / EBP 伪, a protein that regulates gene expression and cell proliferation in the lung tissue. It is also known to play involved in a form of leukemia and liver cancer, squamous skin carcinoma cells, squamous cell cancers of the head and neck and other cancers. in their earlier work, scientists suspected that C / EBP伪 can act as a tumor suppressor in normal cells, but the mechanism by which the absence promoted lung cancer tumors are not clear.
In a series of in vitro experiments, the researchers demonstrated that C / EBP 伪 indeed works as a tumor suppressor by limiting the expression of another molecule known to play a role in triggering and the maintenance of tumor growth. This molecule, Bmi1 is an oncogenic protein that has been implicated in colon cancer, a form of leukemia and breast and gastric cancers.
To determine the relationship between the suspected tumor suppressor (C / EBP 伪) and the oncogenic protein (BMI1), researchers first modified a line of human adenocarcinoma cells to overexpress C / EBP伪. This led to a marked reduction in the expression of BMI1. When the team analyzed tissue from 261 patients with NSCLC, they found an inverse correlation between the two molecules; more than 80 percent of the tissues of patients with low levels of suppression of C / EBP 伪 were positive for expression BMI1 tumor. Similarly, a sample of tissue for analysis from patients with lung adenocarcinoma with little or no C / EBP phrase found that people with lower levels of BMI1 were more likely to survive, a model that has prognostic value, the researchers wrote.
"Our findings suggest that lung cancer subtype defined by the loss of expression of C / EBP could specifically benefit from therapies that inhibit BMI1," the scientists wrote. "Thus, the identification of factors that modulate its expression sparked a major clinical interest."
The research team was also able to validate its findings in mice. In a series of experiments with mice engineered to express any C / EBP 伪, scientists found an inverse relationship between the transcription factor and BMI1 which was almost identical to its human adenocarcinoma data. By manipulating the expression BMI1 in vivo, the researchers were also able to confirm that the decreased expression of the oncogene protein was sufficient to completely inhibit tumor formation and even stop tumor growth significantly.
"BMI1 plays an important role in many solid tumors, including one of the most aggressive models of lung cancer, and its expression is related to tumor growth, invasion, the metastasis, prognosis and recurrence, "said Levantini." Our findings may help us design better therapies for the subset of patients with adenocarcinoma low C / EBP 伪 and high expression pattern BMI1. "
EmoticonEmoticon