Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists find tumor suppressor gene protects against pre-cancerous development

03.11.2006
Cell biologists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have provided further evidence that a gene thought to play a role in suppressing tumors actually can protect against the development of pre-cancerous cell growth as well.

The researchers say that the gene, caveolin-1 (Cav-1), which they found in two major types of breast cells, could be a potential target for future drugs aimed at preventing breast cancer. The work also suggests a potentially important role of the tumor "microenvironment" in the cancerous process.

Cav-1 is involved in breast cancer onset and progression, and it's present in epithelial cells and mammary "fat pads," or stromal cells. The researchers, led by Michael Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and Jefferson's Kimmel Cancer Center, showed striking effects in mice that lacked Cav-1, particularly in stromal cells.

Reporting November 1, 2006 in the American Journal of Pathology, Dr. Lisanti, Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., professor and chair of cancer biology at Jefferson Medical College, and their co-workers showed in a series of experiments that tumor cells grew larger in mammary fat pads lacking Cav-1, and that metastatic breast cancer cells transplanted to fat pads with Cav-1 failed to grow.

"There could also be human conditions where loss of Cav-1 in the stroma could be predisposing patients toward increased risk," Dr. Lisanti says. "This provides the hard genetic evidence of a cause-effect relationship between loss of Cav-1 in the stroma and tumor growth. This could be predictive by looking at Cav-1 in the stroma and seeing if this is a bad risk factor."

The researchers found that mice lacking the Cav-1 gene showed a cell thickening in the breast duct and hyperplasia – or excessive cell growth – in the lobulo-alveolar area. Both are locations where breast cancer can begin.

In one study, they took a tumor from a mouse and put it in a stromal fat pad in both a normal mouse and in a mouse lacking Cav-1 and discovered that the tumor grew twice as large in the latter. "The stroma clearly has effects on normal mammary growth, hyperplasia and tumorigenesis," Dr. Lisanti says.

Dr. Lisanti and his team performed another experiment in which they compared the effects of implanting metastatic breast cancer cells in mice with Cav-1 and those lacking the gene. When they implanted such cells in the mouse flank, which is not a location at which tumors grow, nothing happened. But when they put the cells in the mammary fat pad, tumors formed. When they implanted metastatic breast cancer cells with Cav-1 in the fat pads, "it had a huge effect," Dr. Lisanti says, blocking tumor growth.

"This tumor suppressor effect of Cav-1 depends on the location of the cells," he explains. "This means it is specific to the mammary fat pad. The mammary stromal and epithelial cells somehow sense the microenvironment and respond to the Cav-1 gene."

The researchers believe that the effect also depends on the activity of the cyclin D1 gene, a cancer-causing gene overexpressed in about half of all breast cancers. Using a mouse model of premalignant growth in mice carrying the cyclin D1 gene but lacking Cav-1 – which worsens the condition – the researchers added Cav-1 and found "it completely represses the phenotype, meaning it can not only suppress the tumor, but also the premalignant state caused by cyclinD1 upregulation."

Turning down cyclinD1 activity relies on the cellular microenvironment, Dr. Lisanti says. "We think Cav-1 can block the transforming effects of cyclinD1," he says. "It could be a very important therapeutic candidate for developing caveolin mimetic drugs suppressing cyclinD1 activity."

Dr. Lisanti believes that Cav-1 "could be important for early intervention because patients with epithelial cell hyperplasia could be given Cav-1 mimetic drugs to see if they could suppress this."

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

Further reports about: Cav-1 HDL-cholesterol Lisanti breast cyclinD1 mammary stroma stromal

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 >>>