Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene helps protect tumor suppressor in breast cancer

08.04.2009
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."

PTEN

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:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>