Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lab cell study shows that HOXA5 protein acts as tumor suppressor in breast cancer

20.05.2016

Many breast cancers are marked by a lack of HOXA5 protein, a gene product known to control cell differentiation and death, and lower levels of the protein correspond to poorer outcomes for patients. Now, results of a new study by Johns Hopkins Kimmel Cancer Center scientists suggests a powerful role for the protein in normal breast cells, acting as a tumor suppressor that halts abnormal cell growth.

In their study published online May 9 in the journal Oncogene, scientist Saraswati Sukumar, Ph.D.; her graduate student Wei Wen Teo; and their colleagues show that cells without HOXA5 have an increased capacity to renew themselves and are more invasive than normal breast cells -- in short, they become more tumor like.


A human breast cell lacking HOXA5 (right) shows protruding structures similar to tumor cells, compared with a normal human breast cell (left).

Courtesy of Sara Sukumar, Ph.D.

"Learning more about the biological impact of the HOXA5 protein, which is absent so frequently in breast cancers, may eventually help scientists develop new therapies to treat this disease," says Sukumar.

The loss of HOXA5 leads to an increase in breast cells' "stemness and cell plasticity," meaning they can more easily revert back to an undifferentiated state where they are capable of producing more new cells, says Sukumar, a professor of oncology and pathology at the Johns Hopkins University School of Medicine. Proteins that "promote features of plasticity will allow a tumor to thrive better," she adds.

For the study, the researchers analyzed gene expression from human breast cell lines lacking HOXA5. They found that the protein seems to help maintain several traits in normal breast cells, including the ability to adhere to other epithelial cells, and the presence of molecules marking the cells as differentiated and not capable of self-renewal like breast stem cells.

When Sukumar and the others depleted the HOXA5 protein in other breast cell lines in the lab, the cells became more immature, or "stem like," as well as more mobile. A closer look, she says, revealed that HOXA5 regulates the production of two other proteins: CD24 and E-cadherin. Without CD24, the cells begin to revert toward a stem like state, and without E-cadherin, cells lose some of the "glue" that binds them to other cells, says Sukumar.

As a result, breast cells without HOXA5 were more likely to grow aggressively in lab experiments, forming protruding structures similar to those seen as tumor cells begin to metastasize, the scientists found.

They then tested the behavior of human tumor cells with and without HOXA5 by injecting those cells into the mammary fat pad of mice. Results showed that tumor cells containing the protein carried anywhere from 10 to 17 times fewer breast stem cells, and tumors grown from the injected cells were about three times smaller than those in mice who had received tumor cells with depleted levels of HOXA5.

Sukumar and her colleagues also analyzed data from two international breast cancer genetic data sets and found that the lower the amount of HOXA5 in a tumor, the higher the grade of breast cancer in the patient. Similarly, patients with tumors containing low amounts of HOXA5 protein also had lower cancer relapse-free survival rates.

The scientists are planning further study of HOXA5's role in breast cancer, following up on this work and a study published by Sukumar's lab in 2000 that showed a connection between low levels of HOXA5 and the well-known tumor suppressor protein p53. Sukumar, who is the Barbara B. Rubenstein Professor in Oncology at the Kimmel Cancer Center, recently won a $300,000 grant from the Avon Foundation to continue the work.

###

Other Johns Hopkins scientists who contributed to the study include Vanessa F. Merino, Soonweng Cho, Preethi Korangath, Xiaohui Liang, Ren-chin Wu, Neil M. Neumann, and Andrew J. Ewald.

Funding for the study was provided by the Susan G. Komen Foundation Leadership Grant (SAC110050), the Department of Defense Center of Excellence (W81XWH-04-1-0595), the SKCCC Core grant (P30 CA006973) and the Avon Foundation Center of Excellence.

Media Contact

Vanessa Wasta
wasta@jhmi.edu
410-614-2916

 @HopkinsMedicine

http://www.hopkinsmedicine.org 

Vanessa Wasta | EurekAlert!

Further reports about: CD24 breast cancer breast cells stem cells tumor cells tumor suppressor

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>