Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers Identify Gene That Regulates Breast Cancer Metastasis

07.10.2009
Researchers at The Wistar Institute have identified a key gene (KLF17) involved in the spread of breast cancer throughout the body. They also demonstrated that expression of KLF17 together with another gene (Id1) known to regulate breast cancer metastasis accurately predicts whether the disease will spread to the lymph nodes. Previously, the function of KLF17 had been unknown.

Deaths of most breast-cancer patients are the result of metastasis, a complex, multi-step, and poorly understood process. “Identifying the gene that suppresses the spread of tumor cells and the mechanisms by which this suppression occurs can lead to the discovery of new markers of metastasis and potential targets for cancer prevention and treatment,” says Qihong Huang, M.D., Ph.D., assistant professor at The Wistar Institute and senior author of the study.

In this study, which appears in the October on-line issue of Nature Cell Biology, Huang and colleagues introduced a genetic screen targeting 40,000 mouse genes into mammary tumor cells that do not usually spread, and then transplanted those cells to the mammary fat pads in mice where they would be expected to remain. Through RNA interference (RNAi) technology, they then reduced the expression of a metastasis-suppressor gene in five mice, one of which developed lung metastases in seven weeks. RNA retrieved from the metastasized cells corresponded to KLF17.

To determine whether KLF17 played a similar role in human breast-cancer metastasis, the researchers knocked down KLF17 expression in a tagged human-breast-cancer cell line and then transplanted these cells—along with a control group still expressing KLF17—into mammary fat pads of mice. Within eight to 10 weeks, lung metastases developed in the KLF17-deficient cells, whereas the control cell set did not metastasize, demonstrating that knockdown of KLF17 expression also promotes the spread of human breast-cancer cells.

The researchers also were interested specifically in genes whose expression were increased in KLF17 knockdown cells but decreased in KLF17 overexpressing cells or vice versa. In collaboration with Professor Louise C. Showe, Ph.D. at the Wistar Institute, they found the significant genes that met these criteria. Among them, the gene Id1 was found to be up-regulated in KLF17 knockdown cells and down-regulated in KLF17 overexpressing cells. Recent findings suggest that Id1 is deregulated in various types of cancers and is important in the development of embryonic stem cell–like phenotypes in cancer cells.

To further investigate the interactions of KLF17 and Id1, the Huang lab scanned a DNA segment of mouse Id1 and found two potential KLF17 binding sites. To examine the effect of Id1 upregulation in tumor metastasis in vivo, the team generated tagged mouse and human cell lines expressing mouse or human Id1, respectively. Following transplantation back into the mice, lung metastasis developed from Id1-upregulated cells but not in controls, demonstrating that Id1 expression promotes tumor metastasis in vivo.

Further characterization of KLF17 is an ongoing subject of study for Wistar researchers. “We are continuing to examine ways to activate KLF17 and the methods by which that process slows or prevents cancer metastasis,” Huang says.

The lead author on the study is Wistar’s Kiranmai Gumireddy, Ph.D. Study investigators also included Professor Louise C. Showe, Ph.D.; and Anping Li, from the Wistar Institute; Andres J. Klein-Szanto, M.D.; from Fox Chase Cancer Center; and Phyllis A. Gimotty, Ph.D., Dionyssios Katsaros, M.D., Ph.D.; George Coukos, M.D., Ph.D.; and Lin Zhang, M.D.; from the University of Pennsylvania.

The project was supported by the Breast Cancer Alliance, Pardee Foundation, V Foundation, Commonwealth Universal Research Foundation of the Pennsylvania Department of Health, the National Cancer Institute, and the Mary Kay Ash Charitable Foundation.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures. On the Web at www.wistar.org.

Susan Finkelstein | Newswise Science News
Further information:
http://www.wistar.org

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>