PBX1 identified as a new pioneer factor underlying progression in breast cancer

The presence of a new pioneer factor, known as PBX1, can guide the response to estrogen in breast cancer cells according to researchers at Dartmouth-Hitchcock Norris Cotton Cancer Center in results published on November 17 in the open-access journal PLoS Genetics. This research reveals that PBX1 alone can determine the risk of the spread of cancer in patients with estrogen receptor alpha (ERα)-positive breast cancer, which accounts for about two-thirds of all breast cancers diagnosed in North America.

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. "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," said Dr. Mathieu Lupien, assistant professor of genetics, Norris Cotton Cancer Center, Dartmouth Medical School, who served as principal investigator for the study. Specifically, this research demonstrates that PBX1 directly modulates chromatin compaction at discrete genomic regions to promote the recruitment of the transcription factor ERα, driving the proliferative response to estrogen in breast cancer cells.

"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." said lead author Dr. Luca Magnani, post-doctoral scientist.

"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" said Dr. Lupien.

FINANCIAL DISCLOSURE: This work was supported by NCI (2P30CA023108-32) and the ACS (IRG-82-003-27). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPETING INTERESTS: Patent pending for the use of PBX1 as a biomarker in breast cancer.

CITATION: Magnani L, Ballantyne EB, Zhang X, Lupien M (2011) PBX1 Genomic Pioneer Function Drives ERa Signaling Underlying Progression in Breast Cancer. PLoS Genet 7(11): e1002368. doi:10.1371/journal.pgen.1002368

CONTACT:
Dr. Mathieu Lupien
Principal Investigator.
Mathieu Lupien Lab, HB7936
Dartmouth Hitchcock Medical Center
1 Medical Center Drive
Lebanon, NH, USA, 03756

Email: Mathieu.Lupien@Dartmouth.edu
Telephone: (603) 653-9041
Fax: (603) 653-9952

Contact: Donna Dubuc 603-653-3615
Donna.M.Dubuc@Dartmouth.edu

This press release refers to an upcoming article in PLoS Genetics. The release is provided by journal staff, or by the article authors and/or their institutions. Any opinions expressed in this release or article are the personal views of the journal staff and/or article contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.

PLoS Genetics (http://www.plosgenetics.org) reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology. All works published in PLoS Genetics are open access. Everything is immediately and freely available online throughout the world subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.