Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Understanding IGF-1: Jefferson Researcher Sees Drug Potential in Targeting Enzyme

21.09.2005


He has labored for years over trying to understand and detail the behavior of insulin-like growth factor-1 (IGF-1) receptor, a protein which plays an important role in tumor growth. Several years ago he and his co-workers discovered that normal cells lacking the IGF-1 receptor gene could not be made to turn cancerous. He found that when they “knocked out” IGF-1 receptors in cancer cells, the cells self-destructed, meaning the IGF-1 receptor was somehow necessary for tumor cell growth. Companies are interested in targeting the IGF-1 receptor with the idea of killing cancer cells, he says.



According to Dr. Baserga, who is professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia and acting director of Jefferson’s Kimmel Cancer Center, in the past few years, scientists have learned that the IGF-1 receptor is also a key growth factor that regulates cell and body size. Deleting the genes for the IGF-1 receptor and its docking protein IRS-1 result in mouse and fly embryos that are only 50 percent of normal size.

“This tells you in essence that the IGF-1 receptor and its docking protein control 50 percent of body size in a non-redundant way,” he says. “This was an important finding because it established the role of IGF-1 receptor and IRS-1 in controlling body size.”
Reporting August 19, 2005 in the Journal of Biological Chemistry, Dr. Baserga and his co-workers provide one possible molecular explanation for how this occurs.



They found that when IRS-1 is activated with the IGF-1 receptor, ß-catenin, a protein important in colon and breast cancer is turned on. “We’re the first ones to discover that IRS-1 goes to the cell nucleus, where it binds a protein, ß-catenin, in the nucleus that regulates RNA polymerase 1, the enzyme that controls cell size,” he explains.

He doesn’t think that IRS-1 is the exclusive activator, but rather, one of several. “It makes sense,” he says. “When you knock out the IRS-1 gene, you get flies that are 50 percent in size, so there are other ways to make cells proliferate. Cells without the IGF-1 receptor can grow.”

Several years ago, Dr. Baserga, who pioneered much of the understanding of the basic behavior of the IGF-1 receptor, and his co-workers used knockouts – specially bred mice lacking a particular gene – to develop a cell line without IGF-1 receptors. Normal cells grew, but would not turn cancerous when placed in rodent cells with added cancer-causing genes.

The finding suggested that if cells that lacked IGF-1 receptor could not be turned cancerous, perhaps cancerous cells with IGF-1 could be reversed. “If this is true in humans, then this is a rational target,” he says. Studies by companies in the last few years have found that antibodies and various small molecules made to the IGF-1 receptor kill cancer cells without toxicity, he notes.

“The general idea is that if you find something that knocks out the IGF-1 receptor, you will kill the cancer cells and have only a modest effect on normal cells – at least using cells in culture and in mice,” he says. Several years ago, for example, Dr. Baserga and his group used antisense therapy to target the IGF-1 receptor, which killed cancer cells in mice but didn’t work as well in people. However, clinical trials are just beginning, he says, and he is still hopeful that other approaches will work in humans.

In the meantime, pharmaceutical companies continue to pursue potential drugs and small molecules that target the IGF-1 receptor, and still seek Dr. Baserga’s help.

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

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

25.09.2017 | Trade Fair News

Highest-energy cosmic rays have extragalactic origin

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>