A "pioneer factor" called PBX1 may help scientists understand the causes of breast cancer's resistance to estrogen treatment and help develop new strategies for identifying aggressive tumors, according to a study by researchers at the Norris Cotton Cancer Center. The research, which was conducted in the Dartmouth Medical School professor Mathieu Lupien's lab, was published in the open source journal Public Library of Science Genetics on Nov. 17.
When more PBX1 protein was found in a tumor, there was a greater chance of the tumor metastasizing, or spreading to other parts of the body, according to DMS post-doctoral fellow Luca Magnani, the lead author of the study.
By indicating the aggressiveness of a tumor, PBX1 functions as a marker with clinical applications in determining a patient's prognosis, according Magnani.
"The clinical application is to use it to discriminate which patients are more at risk versus which patients are less at risk," Magnani said. "This is important in deciding which type of therapy to use for each patient."
Through various experiments conducted since August 2009, the researchers determined that PBX1 binds to DNA, allowing the cancer cells to grow and leading to more aggressive tumors, according to Magnani.
The project's original purpose was originally to determine whether an unknown pioneer factor acts as an enabler for breast cancer growth, Magnani said. Using cell line models that mimic the behavior of breast cancer, the team was able to prove the role of PBX1 in promoting breast cancer growth, he said.
Testing for the presence of PBX1 may help clinicians predict the risk of tumor proliferation for patients with estrogen receptor alpha-positive breast cancer, which accounts for about two-thirds of all breast cancers, according to Elizabeth Ballantyne '12, a member of the research team.
The team's findings "may also have therapeutic implications, as PBX1 may be a good target for new treatments to prevent further breast cancer progression in ERA-positive breast cancer," Ballantyne said in an email to The Dartmouth.
Magnani said PBX1 is a "pioneer factor," or type of protein has the ability to bind with DNA that is not accessible to other biochemical factors, he said.
"The way they operate with estrogen receptors is by binding with DNA in order to allow for successive binding," Magnani said.
Very little is known about pioneer factors, according to Magnani. Only one other pioneer factor was identified prior to PBX1's discovery, he said.
The team is currently involved in follow-up research to determine how doctors may target and erase PBX1 to arrest the growth of breast cancer in tumors that are resistant to estrogen treatments, according to Magnani.
An additional study in Lupien's lab is also examining another "suspected pioneer factor that may function similarly to PBX1," Ballantyne said.
"We are trying to find a signature that is telling you your tumor is going to develop resistance, and we are trying to determine how PBX1 is involved in this situation," Magnani said.
The National Cancer Institute and American Cancer Society funded the research, according to the Magnani.
The study's team included Magnani, Ballantyne and DMS PhD candidate Xiaoyang Zhang.
Lupien could not be reached for comment by press time.
