EndocrinologyResearcher Awarded $1.6 Million To Investigate Tumor Suppressor's Role In Breast Cancer
Studies have estimated that five to
ten percent of breast cancer cases in the United States are linked to
inherited mutations, the most common of which are changes in the BRCA1 or
BRCA2 genes. Defects in those genes significantly increase a woman"s
chance of getting breast cancer. Aiming to help unlock the mysteries of
that critical genetic pathway is Bing Xia, PhD, a scientist at The Cancer
Institute of New Jersey (CINJ), who was just awarded $1.6 million from the
National Cancer Institute (NCI), a division of the National Institutes of
Health. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson
Medical School.
The R01 award will support the work of Dr. Xia, an assistant professor of
Radiation Oncology and Pharmacology at UMDNJ-Robert Wood Johnson Medical
School, on the functions of PALB2, another gene that has a critical
function in the same tumor suppression pathway.
BRCA1 and BRCA2 proteins (which are products of the BRCA1 and BRCA2 genes
that carry out their functions) are essential to the maintenance and
repair of DNA -- the material that makes up one"s genes. These proteins
also play important roles in controlling cell growth, particularly after
DNA damage. These functions are considered critical to preventing normal
cells from becoming cancer cells. Therefore defects in BRCA1 or BRCA2
proteins result in approximately a ten-fold increase of lifetime breast
cancer risk. Cancer cells that have non-functional BRCA1 and BRCA2
proteins are unable to repair certain types of DNA damage. Scientists
hope to exploit such vulnerability through the use of specifically
tailored drugs to kill off such cancer cells.
In recent years, Xia and colleagues have discovered that the novel protein
PALB2 serves as a major partner of the BRCA2 protein and that it is
required in BRCA2 DNA damage response function. By virtue of this
essential role in supporting the function of the BRCA2 "tumor suppressor,"
PALB2 appears to be a tumor suppressor in its own right, according to Xia.
He and others have demonstrated that inherited defects in PALB2 cause
heightened risk of breast cancer, just as in the case of BRCA2. Xia"s
team also recently found that PALB2 also binds the other commonly known
breast cancer protein BRCA1, and does so in a way that links the two major
breast cancer proteins to form a central breast cancer suppression
pathway.
In the current project Xia"s team will dig deep into the inner working
mechanisms by which PALB2 operates in the cell to support BRCA2 function
and connect the two BRCA proteins in DNA repair and cell growth control.
They also will generate mouse models of PALB2- and BRCA2-associated breast
cancer to study the path of breast cancer development and the
characteristics of the tumors.
Xia says he is grateful to the NCI for its support and hopes that the
results of the study could have a wide-ranging impact. "This research has
the potential to yield critical insights into the origin and development
of familial breast cancer, and may also shed light on the development of
breast cancer in general," he said. "The results and tools generated from
this study may also contribute to the rational design of new breast cancer
drugs and treatment strategies."
The five-year award period runs through June 30, 2014.
The Cancer Institute of New Jersey