Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New avenue for treating colon cancer

10.02.2012
Research led by UC Riverside cell biologists describes mechanism by which some people may be more susceptible to colon cancer

An international research team led by cell biologists at the University of California, Riverside has uncovered a new insight into colon cancer, the third leading cause of cancer-related deaths in the United States. The research provides potential new avenues for diagnosing and treating the disease.

Led by Frances Sladek at UC Riverside and Graham Robertson at the University of Sydney, Australia, the team analyzed about 450 human colon cancer specimens and found that in nearly 80 percent of them the variants of a gene, HNF4A, are out of balance.

Human beings express several variants of the HNF4A gene, classified as P1 and P2 variants. Some tissues, like liver, have just one type of variant but the colon has both P1 and P2 variants. The P1 variant is found in the nuclei of cells in the normal colon but in the human colon cancer samples this variant is frequently either absent or located outside of the nucleus and, presumably, no longer functional.

Using human colon cancer cell lines and in vitro assays, the researchers found that the imbalance observed in the human tumor tissues seemed to be the result of a complex, multi-step process by an enzyme, Src kinase. Src kinase has been known to be activated in colon cancer but, until now, it was not known to act on the HNF4a protein (HNF4A is the gene, a stretch of DNA; HNF4a is the protein encoded by HNF4A). The UCR group found that activated Src modifies the P1 but not the P2 variant. The net result is loss of the P1 variant in the nuclei of cells in the colon.

Study results appeared online last week in the Proceedings of the National Academy of Sciences.

"Loss of nuclear P1 HNF4a protein in the colon may be an early sign of colon cancer," explained Sladek, a professor of cell biology and toxicologist. "A healthy colon has a good but delicate balance of the two HNF4a variants. If you could prevent the loss of the P1 variant via drugs, you might be able to maintain a normal colon and prevent colon cancer."

The researchers found another factor that increases a person's susceptibility to the disease: certain "single nucleotide polymorphisms" or SNPs located in the HNF4A gene. An SNP is a DNA sequence variation — a minor change in the genomic sequence that accounts for the variations we see between individuals. SNPs are the most common type of genetic variation among people.

"Individuals with certain SNPs may be more susceptible to colon cancer," said Karthikeyani Chellappa, a postdoctoral researcher in Sladek's lab and the first author of the research paper. "That's because these SNPs result in a greater amount of modification and a faster degradation of HNF4a by Src, at least in cell-based assays. It still needs to be investigated, though, whether individuals carrying these SNPs are indeed more susceptible to colon cancer."

Sladek noted that drugs are already available for inhibiting the activity of Src kinase.

"Some of these drugs are in clinical trials for colon cancer," she said. "It would be exciting to determine whether these drugs can maintain the P1 HNF4a protein levels, as well as inhibit the Src kinase activity."

A multifactorial disease influenced by genetics and the environment, colon cancer starts as a small polyp in the large intestine (colon) or the rectum (end of the colon). While most of the polyps are benign, some do turn cancerous. With proper screening, the disease can be detected early, when it is most curable.

Sladek, Chellappa and Robertson were joined in the research by Songqin Pan and Jake M. Schnabl at UCR; Lucy Jankova, Caroline L-S. Fung, Charles Chan, Owen F. Dent and Stephen J. Clarke at the University of Sydney, Australia; and Yann Brelivet of the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. Robertson and the Australian members of the team performed all the analysis of the human tumor samples.

The research was supported in part by a National Institutes of Health grant to Sladek.

The University of California, Riverside (http://www.ucr.edu) is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment has exceeded 20,500 students. The campus will open a medical school in 2013 and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Center. The campus has an annual statewide economic impact of more than $1 billion. A broadcast studio with fiber cable to the AT&T Hollywood hub is available for live or taped interviews. UCR also has ISDN for radio interviews. To learn more, call 951-UCR-NEWS.

Iqbal Pittalwala | EurekAlert!
Further information:
http://www.ucr.edu

More articles from Life Sciences:

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

nachricht The Nagoya Protocol Creates Disadvantages for Many Countries when Applied to Microorganisms
05.12.2016 | Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen 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: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

IHP presents the fastest silicon-based transistor in the world

05.12.2016 | Power and Electrical Engineering

InLight study: insights into chemical processes using light

05.12.2016 | Materials Sciences

High-precision magnetic field sensing

05.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>