According to a study published in November in the open-access journal PLoS Genetics, investigators at Dartmouth-Hitchcock Norris Cotton Cancer Center discovered that the presence of a novel pioneer factor (PBX1) in breast cancer cells can direct the response to estrogen. The study results show that PBX1 alone can establish the risk of cancer spreading in individuals with estrogen receptor alpha (ERα)-positive breast cancer. In North America this type of cancer accounts for approximately two-thirds of all diagnosed breast cancers.
Pioneer factors are a rising group of chromatin remodelers, with the ability to modulate cellular identity arranged by defining the genomic areas accessible for transcription factors.
Dr. Mathieu Lupien, assistant professor of genetics, Norris Cotton Cancer Center, Dartmouth Medical School, who served as lead researcher for the investigation, explained:
“Since cancer is characterized by a loss of cell-fate identity, it is not surprising that other pioneer factors have already been characterized as oncogenic factors in breast cancer, but PBX1 is one that discriminates progression.”
The study shows that PBX1 directly modulates chromatin compaction at discrete genomic areas in order to encourage the recruitment of the transcription factor Erα, powering the proliferative response to estrogen in cancerous cells in the breast.
Lead author Dr. Luca Magnani, post-doctoral scientist, said:
“Unfortunately, numerous ERα-positive patients with breast cancer progress to more advanced stages of the disease as they develop resistance to endocrine therapies, which directly target Erα.”
Dr. Lupien, explained:
“This work may rapidly translate to the clinic because PBX1 could likely serve as a prognostic marker for ERα-positive breast cancer progression. It also highlights the potential therapeutic benefit of developing means to antagonize pioneer factors such as PBX1 to prevent breast cancer progression.”
Written by Grace Rattue