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 Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>