Dartmouth Researchers Identify New Factor in Breast Cancer
November 22, 2011
"Pioneer" factor PBXI underlies metastasis
A new "pioneer" factor, called PBX1, discovered by researchers at Dartmouth-Hitchcock Norris Cotton Cancer Center may help unlock the keys to understanding how breast cancer tumors develop resistance to current therapies. Researchers identified a protein-PBX1-which appears to be related to treatment response. The greater the presence of this protein, the more aggressive a tumor appears to be.
Data suggest that PBX1 may contribute to development of resistance to common estrogen-based treatments for breast cancer. PBX1 may be able to edit and promote the expression of genes that allow the cells to adapt to therapy and become resistant.
"This work may rapidly translate to the clinic as PBX1 can likely serve as a prognostic marker for the positive estrogen receptor alpha (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, Ph.D., assistant professor of genetics, Dartmouth-Hitchcock Norris Cotton Cancer Center, Dartmouth Medical School, who served as principal investigator for the study.
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 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.
"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, Ph.D., post-doctoral scientist, Dartmouth-Hitchcock 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.
About Dartmouth-Hitchcock Norris Cotton Cancer Center
Norris Cotton Cancer Center combines advanced cancer research at Dartmouth College and Dartmouth Medical School with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center, at Dartmouth-Hitchcock regional locations in Manchester and Keene, NH, and St. Johnsbury, VT, and at 11 partner hospitals throughout New Hampshire and Vermont. It is one of 40 centers nationwide to earn the National Cancer Institute's "Comprehensive Cancer Center" designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.