Nav: Home

Breast cancer could be prevented by targeting epigenetic proteins, study suggests

June 19, 2018

Researchers at the Princess Margaret Cancer Centre in Toronto have discovered that epigenetic proteins promote the proliferation of mammary gland stem cells in response to the sex hormone progesterone. The study, which will be published June 19 in the Journal of Cell Biology, suggests that inhibiting these proteins with drugs could prevent the development of breast cancer in women at high risk of the disease.

Mammary glands contain two types of cells, basal and luminal, that arise from specialized stem or progenitor cells. During pregnancy or the menstrual cycle, progesterone induces basal and luminal progenitor cell numbers to expand and drive mammary gland formation. But mammary gland progenitors may also give rise to cancer. Progesterone exposure and stem cell proliferation have been linked to the development of breast cancer, and the number of progenitor cells is often elevated in women carrying mutations in BRCA1 or other genes that put them at a high risk of developing the disease.

"Currently, there are no standard of care preventative interventions for women at high risk of breast cancer," says Dr. Rama Khokha, a Senior Scientist at Princess Margaret Cancer Centre and Professor of Medical Biophysics at the University of Toronto. "Although it is becoming increasingly clear that stem and progenitor cells underlie cancer development, we lack strategies to target these cells for chemoprevention."

To learn more about these progenitor cells and identify any vulnerabilities that could potentially be exploited to prevent the development of breast cancer, Khokha and colleagues isolated cells from the mammary glands of mice and examined how they changed in response to progesterone. The researchers had previously measured all of the RNA molecules produced by mammary gland cells. Now they quantified all of the cells' proteins and assessed the cells' epigenomes--the various chemical modifications to a cell's chromosomes that help determine which genes are turned on and off.

This global overview of mammary gland cells revealed that in response to progesterone, progenitor cells--particularly luminal progenitor cells--up-regulate many of the epigenetic regulatory proteins responsible for modifying the cells' chromosomes.

"We thought that drugs that inhibit these epigenetic regulatory proteins might suppress the proliferation of stem and progenitor cells in response to progesterone," Khokha says.

The researchers tested multiple epigenetic inhibitors, many of which are already approved for use in humans by the FDA. Several of these drugs inhibited the proliferation of mammary gland progenitor cells and decreased their total number in mice. One, a drug called decitabine that inhibits DNA methyltransferase enzymes and is approved to treat myelodysplastic syndrome, delayed the formation of tumors in breast cancer-prone rodents.

Khokha and colleagues then tested the effects of epigenetic inhibitors on mammary gland progenitor cells isolated from women at high risk of developing breast cancer. Progenitor cells from patients with BRCA1 mutations were particularly vulnerable to epigenetic inhibitors, including decitabine. Decitabine also suppressed the activity of progenitor cells from patients with mutations in the BRCA2 gene.

"This demonstrates that the dependency of progenitor cells on specific epigenetic proteins is conserved between mice and humans and highlights the potential of epigenetic therapies to target these important cell types in the human breast as a form of chemoprevention," says Khokha.
-end-
Casey et al., 2018. J. Cell Biol.http://jcb.rupress.org/cgi/doi/10.1083/jcb.201804042?PR

About the Journal of Cell Biology

The Journal of Cell Biology (JCB) features peer-reviewed research on all aspects of cellular structure and function. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JCB makes all of its content free online no later than six months after publication. Established in 1955, JCB is published by the Rockefeller University Press. For more information, visit http://jcb.rupress.org/.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JCB on Twitter at @JCellBiol and @RockUPress.

Rockefeller University Press

Related Breast Cancer Articles:

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.
Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.
More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.
Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.
Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.
Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.
Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.
Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.
Does MRI plus mammography improve detection of new breast cancer after breast conservation therapy?
A new article published by JAMA Oncology compares outcomes for combined mammography and MRI or ultrasonography screenings for new breast cancers in women who have previously undergone breast conservation surgery and radiotherapy for breast cancer initially diagnosed at 50 or younger.
Blood test offers improved breast cancer detection tool to reduce use of breast biopsy
A Clinical Breast Cancer study demonstrates Videssa Breast can inform better next steps after abnormal mammogram results and potentially reduce biopsies up to 67 percent.
More Breast Cancer News and Breast Cancer Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.