PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Protein complex plays role in suppressing pancreatic tumors, Stanford study shows

2012-01-10
(Press-News.org) STANFORD, Calif. — A well-known protein complex responsible for controlling how DNA is expressed plays a previously unsuspected role in preventing pancreatic cancer, according to researchers at the Stanford University School of Medicine.

Technological advances in the way researchers can compare normal and tumor DNA showed that the gene for at least one subunit of the multi-subunit SWI/SNF protein complex was either deleted, mutated or rearranged in about a third of the 70 human pancreatic cancers that the Stanford team examined. Additionally, the researchers found that restoring the expression of one of the missing genes slowed the growth of pancreatic cancer cells in the laboratory and caused them to enter an arresting state called senescence.

"This is really strong genetic evidence that this complex plays a role in pancreatic cancer," said associate professor of pathology Jonathan Pollack, MD, PhD, "and it suggests the influence of the SWI/SNF complex is on par with that of other well-known tumor suppressors, such as p53."

Pollack is the senior author of the research, which will be published online Jan. 9 in the Proceedings of the National Academy of Sciences. Graduate student Hunter Shain is the first author.

The tumor-suppressing role of the SWI/SNF complex had not been previously discovered because the disabling changes were spread among five of the complex's protein subunits. In other words, one person's pancreatic cancer might have a mutation or deletion in one protein subunit, while another's could have a change in a different subunit. Considered individually, each variation occurs relatively infrequently.

Shain and Pollack used a technique called array comparative genomic hybridization, or CGH, to pinpoint places in the genome that differed among normal and cancerous pancreatic epithelial cells. The procedure relies on the ability of single-stranded DNA to seek out and bind to its mirror image. By comparing the relative amounts of tumor and normal DNA that bind to a panel of reference sequences, the researchers can tell whether the cancer cell contains amplifications or deletions of genetic material in specific regions throughout the genome. These copy-number variations often occur in genes or regions important in regulating uncontrolled cell growth.

The researchers examined about 70 different pancreatic cancers, including specimens provided by their co-authors at the Sol Goldman Pancreatic Cancer Research Center at the Johns Hopkins University School of Medicine. Forty-eight of the cancers were primary samples from human patients that had been coaxed to grow in immune-deficient mice; 22 had been maintained as laboratory-grown cancer cell lines. Shain used high-density arrays of reference DNA sequences for the CGH, which allowed him to identify amplified or deleted regions at a much higher resolution than previously possible — narrowing the areas of interest to just a few thousand nucleotides rather than larger stretches of DNA.

When the researchers looked at the results of the array CGH analysis, they found many genes known to be involved in pancreatic cancer, and also some new candidates. In particular, they noticed that the genes for individual subunits of the SWI/SNF complex were altered in about 5 to 10 percent of the cancer samples — an interesting finding, but not prevalent enough to spark further immediate investigation under normal circumstances. However, when considered together, Shain and Pollack realized that more than a third of the cancer samples contained a deletion, mutation or rearrangement in the gene for at least one of the five subunits.

"Our intention was to identify new genes involved in pancreatic cancer," said Pollack. "The discovery that SWI/SNF plays a role was exciting because we never would have found it any other way. It really validates the use of genome-wide analysis."

The researchers then experimented with artificially increasing the expression of the gene for one of the subunits in cancer cells in which it was deleted. They found that, in the laboratory, these pancreatic cancer cells engineered to re-express the missing protein slowed their growth and even began to senesce, or enter a permanently arrested state, rather than dividing uncontrollably.

The involvement of SWI/SNF in pancreatic cancer is both exciting and challenging because of its global effect on gene expression. DNA is normally packaged tightly around bundles of protein called histones, and the combination of DNA and proteins is called chromatin. SWI/SNF works by repositioning histones on DNA to make it available for transcription factors that govern DNA's use as a template for the synthesis of RNA, which goes on to serve as a template for the proteins to do the work of the cell.

"We're becoming more and more aware that chromatin modification and remodeling play an important role in cancer," said Pollack, pointing out that several other recent studies have also zeroed in on proteins controlling the architecture of the genome. "What we'd like to learn now is specifically how altering this particular complex affects cancer progression. The major effect is likely to be through changes in the expression of genes."

The researchers are now working to pinpoint exactly which genes are important to drive the growth of human pancreatic cells by artificially overexpressing or blocking the expression of genes coding for various SWI/SNF subunits.

###

In addition to Shain and Pollack, other Stanford researchers involved in the study include graduate student Craig Giacomini and former pathology resident Karen Matsukuma, MD, PhD.

The research was supported by the National Cancer Institute and the Lustgarten Foundation.

Information about Stanford's Department of Pathology, which also supported the work, is available at http://pathology.stanford.edu/.

The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://mednews.stanford.edu. The medical school is part of Stanford Medicine, which includes Stanford Hospital & Clinics and Lucile Packard Children's Hospital. For information about all three, please visit http://stanfordmedicine.org/about/news.html.

PRINT MEDIA CONTACT: Krista Conger at (650) 725-5371 (kristac@stanford.edu)
BROADCAST MEDIA CONTACT: M.A. Malone at (650) 723-6912 (mamalone@stanford.edu)

END



ELSE PRESS RELEASES FROM THIS DATE:

Dabigatran associated with increased risk of acute coronary events

2012-01-10
CHICAGO – The anticoagulant dabigatran is associated with an increased risk of myocardial infarction (heart attack) or acute coronary syndrome in a broad spectrum of patients when tested against some other medicines, according to a study published Online First by the Archives of Internal Medicine, one of the JAMA/Archives journals. "Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran," the study concludes. Dabigatran etexilate was approved by the European Medicines Agency in 2008 for prevention of venous thromboembolism ...

Statin use in postmenopausal women associated with increased diabetes risk

2012-01-10
CHICAGO – The use of statins in postmenopausal women is associated with increased diabetes risk, according to a study published Online First by the Archives of Internal Medicine, one of the JAMA/Archives journals. But researchers note statins address the cardiovascular consequences of diabetes and current American Diabetes Association guidelines for primary and secondary prevention should not change. Likewise, researchers write that guidelines for statin use in nondiabetic populations also should not change. Annie L. Culver, B. Pharm, Rochester Methodist Hospital, Mayo ...

Payment review of emergency department eye care in Florida

2012-01-10
CHICAGO – A substantial proportion of emergency department eye care in Florida is reimbursed through Medicaid or paid for out of pocket by patients, and those findings may help in strategic planning as the debate over how best to implement the nation's new health care reform law progresses, according to a study published in the Archives of Ophthalmology, one of the JAMA/Archives journals. The Patient Protection and Affordable Care Act (PPACA) will increase insurance coverage in large part by expanding eligibility for Medicaid, "an already stressed and underfunded system ...

Replacing Medicare visual acuity screening with dilated eye exams appears cost effective

2012-01-10
CHICAGO – Replacing visual acuity screenings for new Medicare enrollees with coverage of a dilated eye exam for healthy patients entering the government insurance program for the elderly "would be highly cost-effective," suggests a study being published Online First by the Archives of Ophthalmology, one of the JAMA/Archives journals. People can enroll in Medicare after they turn 65 and are supposed to receive a visual acuity screening and other preventive health checks as part of a Welcome to Medicare health evaluation within 12 months of enrollment. In 2009, the U.S. ...

Study confirms new strategy in fight against infectious diseases

2012-01-10
COLUMBUS, Ohio – New research shows that infectious disease-fighting drugs could be designed to block a pathogen's entry into cells rather than to kill the bug itself. Historically, medications for infectious diseases have been designed to kill the offending pathogen. This new strategy is important, researchers say, because many parasites and bacteria can eventually mutate their way around drugs that target them, resulting in drug resistance. In this study, scientists showed that using an experimental agent to block one type of an enzyme in cell cultures and mice prevented ...

Study finds nicotine patches may help improve memory loss in older adults

2012-01-10
Wearing a nicotine patch may help improve memory loss in older adults with mild cognitive impairment, according to a study published today in Neurology, the medical journal of the American Academy of Neurology. The study looked at individuals with mild cognitive impairment (MCI), the stage between normal aging and dementia when others begin to notice that an individual is developing mild memory or thinking problems. Many older adults with MCI go on to develop Alzheimer's disease. The study looked at 74 non-smokers with MCI and an average age of 76. Half of the patients ...

A penny-per-ounce tax on sugar-sweetened beverages keeps the doctor away and saves money

2012-01-10
Over the past 10 years, Americans drank more sugar-sweetened beverages than ever—as much as 13 billion gallons a year—making these drinks the largest source of added sugar and excess calories in the American diet and, arguably, the single largest dietary factor in the current obesity epidemic. While many states have a sales tax on soda, experts believe they are too low to impact consumption. In a study conducted at Columbia University Medical Center and the University of California, San Francisco, researchers estimated that if a higher, penny-per-ounce tax were imposed ...

Legionnaires' disease outbreak linked to hospital's decorative fountain

2012-01-10
CHICAGO -- A 2010 outbreak of Legionnaires' disease in Wisconsin has been linked to a decorative fountain in a hospital lobby, according to a study published in the February issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America. When the outbreak of Legionnaires' disease was detected among eight people in southeast Wisconsin, state and local public health officials worked closely with hospital staff to launch an investigation to determine the source of the outbreak. Legionnaires' disease is a severe and ...

New research helps predict bat presence at wind energy facilities

2012-01-10
ALBANY, Calif. -- An interactive tool developed by researchers from the USDA Forest Service's Pacific Southwest Research Station (PSW) will help wind energy facility operators make informed decisions on efficient ways to reduce impacts on migratory bats. Fatalities of migratory bats at wind energy facilities have become a frequent occurrence. Bat migration patterns are poorly understood and the relationship between fatalities at wind energy facilities and migratory behavior are still being studied. Previous research has shown that adjusting the operations of turbines ...

Scientists solve mystery of colorful armchair nanotubes

2012-01-10
Rice University researchers have figured out what gives armchair nanotubes their unique bright colors: hydrogen-like objects called excitons. Their findings appear in the online edition of the Journal of the American Chemical Society. Armchair carbon nanotubes – so named for the "U"-shaped configuration of the atoms at their uncapped tips – are one-dimensional metals and have no band gap. This means electrons flow from one end to the other with little resistivity, the very property that may someday make armchair quantum wires possible. The Rice researchers show armchair ...

LAST 30 PRESS RELEASES:

Being physically active, even just a couple of days a week, may be key to better health

High-fat diet promote breast cancer metastasis in animal models

A router for photons

Nurses and AI collaborate to save lives, reduce hospital stays

Multi-resistance in bacteria predicted by AI model

Tinker Tots: A citizen science project to explore ethical dilemmas in embryo selection

Sensing sickness

Cost to build multifamily housing in California more than twice as high as in Texas

Program takes aim at drinking, unsafe sex, and sexual assault on college campuses

Inability to pay for healthcare reaches record high in U.S.

Science ‘storytelling’ urgently needed amid climate and biodiversity crisis

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

[Press-News.org] Protein complex plays role in suppressing pancreatic tumors, Stanford study shows