Breast cancer is the second most common cancer among women in the
United States, after skin cancer. Ovarian cancer is the fifth leading
cause of cancer death among women, according to the National Cancer
Defects in a key gene - long thought to drive cancer by turning off
the protection afforded by the well-known BRCA genes - spur cancer
growth on their own, suggested a study led by researchers from NYU
Langone Medical Center.
‘When normal, EMSY, BRCA1 and BRCA2 give the body's cells instructions to create proteins that help to repair DNA damage that can cause cancer. When those genes are altered, the repair process fails and cancer grows.’
The study gene, known as EMSY, has some of the same functions as
BRCA1 and BRCA2, which are known to protect against breast and ovarian
cancer when normal. When defective, BRCA genes block the body's
self-defense against cancer-causing genetic mistakes.
The new study, published online in Oncotarget
helps to explain why some women with healthy BRCA1 and BRCA2 genes
develop cancer. The findings may also expand treatment options for the
roughly 11% of women with breast and ovarian cancer and normal
BRCA genes, say the study authors.
"Now that we know exactly how changes in EMSY spur cancer cell
growth, we can start to design therapies to specifically target that
activity and hopefully stop it," says senior author Douglas Levine, director of the Division of Gynecologic Oncology at NYU Langone and its
Perlmutter Cancer Center.
"This work also suggests that treatments that work for patients with
BRCA1 or BRCA2 mutations might also be effective against EMSY-driven
cancers because the disease mechanism is similar," says first study
author Petar Jelinic, a research assistant professor at NYU
Langone. "The best way to go rapidly from bench to bedside is to find
new ways to use existing treatments."
When normal, EMSY, BRCA1 and BRCA2 give the body's cells
instructions to create proteins that help to repair DNA damage that can
cause cancer. When those genes are altered, the repair process fails and
cancer grows. Overly active EMSY, like mutated BRCA1 or BRCA2, changes
those instructions, so that the DNA damage repair process is blocked.
This new study dispels prior theories that EMSY's activation merely
turned off the cancer suppression function of BRCA2, says Jelinic.
Earlier work by Levine and others pointed toward EMSY activation as a
culprit in breast and ovarian cancer, but had only examined certain
parts of the EMSY protein. The new study was the first to evaluate the
full-length EMSY protein and to show that it acts independently of BRCA1
Furthermore, the research revealed the part of the EMSY protein is
changed by an enzyme called protein kinase A. When there is more active
EMSY than normal, this enzyme reacts with the EMSY protein to more
thoroughly suppress the DNA repair process.