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Dartmouth Researchers Identify a New Pioneer Factor

PBX1 Underlies Metastasis in Breast Cancer

A new pioneer factor, known as PBX1, guides the transcriptional response to estrogen in breast cancer cells, according to epigenetic researchers at Norris Cotton Cancer Center and as reported today in PLoS Genetics.

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(l to r) Elizabeth Ballantyne; Mathieu Lupien, PhD; Luca Magnani, PhD; and Xiaoyang Zhang

Their research reveals that PBX1 alone can discriminate the risk of metastasis in estrogen receptor alpha (ERα) breast cancer patients, which accounts for two-thirds of all breast cancers diagnosed in North America.

"This work may rapidly translate to the clinic, as PBX1 can 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" said Mathieu Lupien, PhD, assistant professor of genetics, Norris Cotton Cancer Center, Dartmouth Medical School, who served as principal investigator for the study.

A Pioneer Factor that Discriminates Progression

Pioneer factors are an emerging class of chromatin remodelers with the capacity to modulate cellular identity as they set the stage by defining the genomic regions accessible for transcription factors.

Photo: Mathieu Lupien, PhD, at his lab bench

Mathieu Lupien, PhD, at his lab bench

"Since cancer is characterized by a loss of cellular 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," said Dr. Lupien. Specifically, the study demonstrates that PBX1 directly modulates chromatin compaction at discrete genomic regions to promote the recruitment of the transcription factor ERα, which drives the proliferative response to estrogen in breast cancer cells.

A Step Closer to Finding a Cure

"Unfortunately, numerous ERα-positive breast cancer patients progress to more advanced stages of the disease as they develop resistance to endocrine therapies, which directly target ERα." said lead author Luca Magnani, PhD, post-doctoral scientist, Norris Cotton Cancer Center. "This work brings us a step closer to finding a cure."

Lupien’s research team included Magnani, Elizabeth Ballantyne, and Xiaoyang Zhang.

November 18, 2011