Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene helps protect tumor suppressor in breast cancer

Researchers find Rak regulates PTEN, may work independently as well

Scientists at The University of Texas M. D. Anderson Cancer Center have discovered a gene that protects PTEN, a major tumor-suppressor that is reduced but rarely mutated in about half of all breast cancers.

The gene Rak helps protect and regulate PTEN, which also is important in several other types of cancer, the team reports in the April edition of Cancer Cell. Causes for diminished PTEN protein levels in breast cancer absent a mutation of the PTEN gene have eluded researchers, who knew for several years that a piece of the puzzle was missing.

"We've clearly discovered the missing link that explains how Rak can stabilize PTEN protein to prevent breast cancer development," said lead author Shiaw-Yih Lin, Ph.D., an assistant professor in the Department of Systems Biology at M. D. Anderson. "Our research explains why PTEN is defective in breast cancer and provides important clues for the development of effective therapy in Rak- or PTEN-defective breast cancers."

In addition to breast cancer, PTEN frequently is mutated or inactivated in glioblastoma, melanoma, and cancers of the prostate and endometrium. The severity of PTEN irregularities strongly correlates with the tumor stage and grade. For example, complete loss of PTEN expression is found more frequently in metastatic cancer than in primary tumors.

In the laboratory, researchers found Rak can stabilize PTEN protein and function as a tumor suppressor gene to prevent breast cancer development.

To examine the correlation between Rak and PTEN protein expression, researchers analyzed cells from 42 breast cancers. Rak expression showed a strong positive correlation with PTEN.

They also investigated the effect of Rak expression by injecting mice with cells that over-expressed Rak. All the mice injected with Rak-overexpressing cells remained tumor free, whereas all the control mice developed tumors.

"To further assess whether Rak is a bona fide breast tumor suppressor gene, we sought to determine if loss of Rak expression would transform normal mammary epithelial cells," Lin said. "We injected control cells or cells in which Rak was compromised into the mammary glands of healthy mice and monitored tumor growth. Notably, all the mice injected with Rak-knockdown cells, but none of the mice injected with control cells, developed tumors."

Recent studies have shown that the PTEN protein is destroyed when it is bound by the enzyme NEDD4-1, which attaches targeting molecules called ubiquitins that mark PTEN for destruction by the ubiquitin proteasome complex.

Lin and colleagues showed that Rak saves PTEN from degradation by attaching a phosphate group to the protein, blocking NEDD4-1 from binding to PTEN.

Although this study demonstrates a PTEN-dependent function of Rak, Lin says much research remains ahead on yet-unidentified PTEN-independent functions of Rak in tumor suppression.

"Recently, we found that Rak can prevent spontaneous DNA damage and has a critical role in suppressing cancer stem cells," he said. "So, we will expand our research efforts toward determining how Rak helps to maintain genomic integrity."


This work was supported in part by a grant from the National Cancer Institute.

In addition to Lin, other authors on the study included Eun-Kyoung Yim, Ph.D., Guang Peng, M.D., Ph.D., Hui Dai, M.D., Ruozhen Hu, M.S., Yiling Lu, M.D., and Gordon Mills, M.D., Ph.D. of the Department of Systems Biology at M. D. Anderson; Kaiyi Li, Ph.D. of the Department of Surgery at Baylor College of Medicine, Funda Meric-Bernstam, M.D. of the Department of Surgical Oncology at M. D. Anderson; Bryan Hennessy, M.D. of the Department of Gynecologic Medical Oncology at M. D. Anderson; and Rolf Craven, Ph.D. of the Department of Molecular and Biomedical Pharmacology at the University of Kentucky, Lexington.

Scott Merville | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

TRAPPIST-1 planets provide clues to the nature of habitable worlds

21.03.2018 | Physics and Astronomy

The search for dark matter widens

21.03.2018 | Materials Sciences

Natural enemies reduce pesticide use

21.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>