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

Study redefines role of estrogen in cervical cancer

2015-06-09
(Press-News.org) MADISON, Wis. -- Scientists have prior evidence that the hormone estrogen is a major driver in the growth of cervical cancer, but a new study examining genetic profiles of 128 clinical cases reached a surprising conclusion -- estrogen receptors all but vanish in cervical cancer tumors.

This counterintuitive finding, reported June 8 in the online Proceedings of the National Academy of Sciences, further bolsters the understanding of cervical cancer's progression and offers valuable new targets to fight the disease.

Lead author Johan den Boon, associate scientist with the Morgridge Institute for Research at the University of Wisconsin-Madison, says the research team used gene expression profiling on 128 specimens from the Study to Understand Cervical Cancer Early Endpoints and Determinants, or SUCCEED. More than 4,000 women are participating in the SUCCEED study, a major effort to understand the second-leading cause of cancer in women globally. It is led by the National Cancer Institute (NCI) and the University of Oklahoma Health Sciences Center.

Virtually all cervical cancers derive from human papillomavirus (HPV) infection. The specimens in this study came from four distinct groups -- healthy patients, patients with either early or advanced complications due to HPV infection, and those with cervical cancer. Den Boon says these four groups allowed researchers to study the full progression from viral infection to cancer -- a unique opportunity among human cancers.

'Our top goal is to find genetic signatures that will predict what early stages of HPV infection are most likely to become cancerous, and what stages we need to worry less about,' says den Boon, of the Morgridge Virology team led by University of Wisconsin-Madison and Morgridge scientist Paul Ahlquist.

A hallmark of HPV-associated disease is a dramatic increase in levels of a protein called p16, which normally is involved in regulating cell division. In profiling gene expression in the 128 specimens, the study posed the question: What other genes might be behaving like p16? This is where authors encountered the surprise estrogen receptor expression. 'It does the complete opposite of p16,' den Boon says. 'Estrogen receptor is in the healthy cells. But as the cells become cancerous, the levels of estrogen receptor alpha crash to the point of being undetectable.'

Den Boon says the team was 'stunned' by the finding and at first assumed there was a flaw in the study. 'P16 and estrogen were as polar opposite as you can get. When looking at similarities between the 54,000 measurements we have on the human genome, p16 would be number one and estrogen would be 54,000.'

Other measurements for hundreds of other genes that respond to estrogen made it clear that levels of the estrogen receptor and of the genes it controls are a powerful marker for cervical cancer progression, he says.

The group conducted microscopic analysis of the samples for further insights. Here, they observed that while estrogen receptor was absent in cancer cells, it was prevalent and in many cases increased in the so-called tumor microenvironment -- the area around the tumor that helps it grow.

The finding highlights that something critical is happening between the microenvironment and the tumor itself, allowing the tumor to thrive in spite of its inability to 'see' estrogen. 'If we want to understand the role of estrogen, we now have to look at how the tumor and the microenvironment communicate with one another,' den Boon says.

The next phase of this puzzle is under way. Postdoctoral fellow Omid Forouzan, who is in a joint position at Morgridge and with UW-Madison biomedical engineer David Beebe, will lead the tumor signaling project. The project will rely on microfluidics techniques pioneered by Beebe.

'What David's group can do is grow populations of cells in a very miniaturized state in ways that they can reach out and talk to each other through tiny channels, but yet they stay distinct,' den Boon says.

One could think of it as molecular espionage. The project will attempt to intercept the biochemical signals that are going back and forth between the microenvironment and the tumor. This is where small molecule therapeutics could be developed to interfere with the signals and suppress tumor growth.

Cervical cancer, which used to be the leading cause of cancer deaths for women in the United States, is a medical success story in developed nations. Thanks to widespread early screening via Pap tests and the availability of an HPV vaccine, rates in the U.S. are down to about 12,000 cases and 4,000 deaths annually.

But it remains a major threat globally, with more than 500,000 new cases per year -- about half of which will be fatal. It's the third leading cause of cancer deaths for women worldwide. Early detection and treatment of lesions caused by HPV can all but eliminate the onset of cervical cancer, but many countries do not have access to early screening tests. Further, the HPV vaccines are among the most expensive vaccines available and their implementation is far from complete.

This study offers another avenue to target and alter the disease progression. Since estrogen also plays an important role in other cancers, including breast cancer and prostate cancer, den Boon says this work has the potential to benefit other cancer-fighting efforts.

INFORMATION:

Funding for the project comes from the National Institutes of Health and the Morgridge Institute. Ahlquist, a fellow of the Howard Hughes Medical Institute (HHMI), worked closely on the project with Nico Wentzensen of the NCI and Joan Walker at the University of Oklahoma.

Other Madison contributors include Mark Horswill from Morgridge; Paul Lambert from the UW-Madison McArdle Laboratory for Cancer Research; and Rachel Pearson and Meghan Scott from the UW-Madison Institute for Molecular Virology.

Contact:

Brian Mattmiller
bmattmiller@morgridge.org
608-316-4332

Johan den Boon
jdenboon@morgridge.org
608-316-4462



ELSE PRESS RELEASES FROM THIS DATE:

NREL's economic impact tops $872 million

2015-06-09
The economic impact of the Energy Department's National Renewable Energy Laboratory (NREL) was $872.3 million nationwide in fiscal year 2014, according to a study by the University of Colorado Boulder's Leeds School of Business. The study estimates NREL's impact to Colorado's economy totaled $701 million, a decline of 1.6 percent from the prior year. The slight year-over-year drop was largely attributed to a decline in major construction spending that came as NREL completed the planned build-out of its sustainable campus. Jefferson County, where the largest concentration ...

NREL, Clemson University collaborate on wind energy testing facilities

2015-06-09
Two of our nation's most advanced wind energy research and test facilities have joined forces to help the wind energy industry improve the performance of wind turbine drivetrains and better understand how the turbines can integrate more effectively with the electrical grid. Through a Cooperative Research and Development Agreement (CRADA), the Energy Department's National Renewable Energy Laboratory (NREL) and Clemson University will partner to share resources and capabilities in the operation and development of testing facilities. The CRADA also includes the exchange ...

Mentorship a key factor for female authorship in GI

2015-06-09
DOWNERS GROVE, Ill. - June 9, 2015 - The percentage of U.S. female physician authors of original research in major gastroenterology journals has grown over time, yet the percentage of women in the senior author position remains lower than expected based on the proportion of female gastroenterologists in academia. A look at the evolution of gender in the GI publishing landscape is presented in "Female authorship in major academic gastroenterology journals: a look over 20 years," published in the June issue of GIE: Gastrointestinal Endoscopy, the monthly peer-reviewed scientific ...

'Myths' persist about the increase in human-caused seismic activity

2015-06-09
SAN FRANCISCO--Seismologists studying the recent dramatic upswing in earthquakes triggered by human activity want to clear up a few common misconceptions about the trend. There is increasing evidence that these earthquakes are caused by injecting fluids from oil and gas operations deep into the earth. These human-caused earthquakes are sometimes called "induced earthquakes." A Seismological Research Letters focus section to be published online June 10 addresses some common misconceptions about induced seismicity--the biggest of which is that it is primarily related ...

Stem cell discovery paves way for targeted treatment for osteoarthritis

2015-06-09
Scientists at the University of York have made a significant advance that could make cell-based treatments for arthritis less of a lottery. Researchers in the Departments of Biology and Physics at York, working with colleagues at the Erasmus Medical Centre in Rotterdam, have identified individual stem cells that can regenerate tissue, cartilage and bone. The stem cells are mixed within human bone marrow stromal cells (MSCs) but are similar in appearance and previously, scientists had difficulty in distinguishing between them. The York researchers isolated individual MSCs ...

How a gut feeling for infection programs our immune response

2015-06-09
An unexpected finding by an international team of scientists based at The University of Manchester and National Institutes of Health in America has shed new light on how immune cells are programmed to either repair or protect the body. It's hoped the discovery will inform the development of better treatments for a range of conditions from inflammatory bowel diseases (IBD) to certain cancers. The research, led by Dr John Grainger from the Manchester Collaborative Centre for Inflammation Research (MCCIR) and Dr Yasmine Belkaid from the National Institute of Allergy and ...

New tool could predict large solar storms more than 24 hours in advance

New tool could predict large solar storms more than 24 hours in advance
2015-06-09
Large magnetic storms from the Sun, which affect technologies such as GPS and utility grids, could soon be predicted more than 24 hours in advance. Coronal mass ejections (CMEs) are eruptions of gas and magnetised material from the Sun that have the potential to wreak havoc on satellites and Earth-bound technologies, disrupting radio transmissions and causing transformer blowouts and blackouts. These mass ejections can cause problems with GPS technology - used by all kinds of vehicles, from cars to oil tankers to tractors. For example, they can affect the ability of ...

West African Ebola virus strain less virulent than prototype 1976 strain

2015-06-09
What: The Makona strain of Ebola virus (EBOV) circulating in West Africa for the past year takes roughly two days longer to cause terminal disease in an animal model compared to the original 1976 Mayinga strain isolated in Central Africa, according to a new National Institutes of Health (NIH) report. The results provide important information to scientists who have wondered if the Ebola virus in West Africa is becoming more severe. In fact, the new study suggests the current virus has a decreased ability to cause disease in their animal model compared to the 1976 strain. Using ...

Discovering a new force driving cell contraction during development and organogenesis

Discovering a new force driving cell contraction during development and organogenesis
2015-06-09
This news release is available in Spanish. CRG scientists describe a new mechanism shaping cells and generating cell contractile forces during development and organogenesis. The new mechanism, which has been published today in the journal Developmental Cell, includes strategies shared with programmed cell death but which have not previously been directly associated with force generation. Studying developmental processes such as the one presented in the Dev. Cell paper contributes to a better understanding of organ development and maintenance. Also, ...

For safer care, simple steps yield substantial improvements in colorectal surgery

2015-06-09
Simple steps that include the consistent use of experienced medical teams for a single type of surgery, preemptive antibiotics before the procedure, less reliance on potent opioids during recovery and urging patients to get out of bed and move around sooner can not only prevent infections, blood clots and other serious complications in people undergoing colorectal operations, but can also accelerate recovery and reduce cost of care, according to results of an ongoing program at The Johns Hopkins Hospital. The approach, dubbed Integrated Recovery Pathway, or IRP, and its ...

LAST 30 PRESS RELEASES:

Heat and heavy metals are changing the way that bees buzz

What’s behind the enormous increase in early-onset gastrointestinal cancers?

Pharmacogenomics expert advances precision medicine for bipolar disorder

Brazilian researcher explores centenarian stem cells for aging insights

Dr. Xuyu Qian's breakthrough analysis of 18 million brain cells advances understanding of human brain development

Gene networks decode human brain architecture from health to glioma

How artificial light at night damages brain health and metabolism

For ultrasound, ultra-strength not always a good thing

Matching your workouts to your personality could make exercising more enjoyable and give you better results

Study shows people perceive biodiversity

Personality type can predict which forms of exercise people enjoy

People can accurately judge biodiversity through sight and sound

People diagnosed with dementia are living longer, global study shows

When domesticated rabbits go feral, new morphologies emerge

Rain events could cause major failure of Waikīkī storm drainage by 2050

Breakthrough in upconversion luminescence research: Uncovering the energy back transfer mechanism

Hidden role of 'cell protector' opens cancer treatment possibilities

How plants build the microbiome they need to survive in a tough environment

Depression due to politics and its quiet danger to democracy addressed in new book 'The Sad Citizen'

International experts and patients unite to help ensure all patients are fully informed before consenting to new surgical procedures

Melting glaciers could trigger more explosive eruptions globally, finds research

Nearly half of U.S. grandchildren live within 10 miles of a grandparent

Study demonstrates low-cost method to remove CO₂ from air using cold temperatures, common materials

Masonic Medical Research Institute (MMRI) welcomes 13 students to prestigious Summer Fellowship program

Mass timber could elevate hospital construction

A nuanced model of soil moisture illuminates plant behavior and climate patterns

$2.6 million NIH grant backs search for genetic cure in deadly heart disease

Pennsylvania’s medical cannabis program changed drastically when anxiety was added as a qualifying condition

1 in 5 overweight adults could be reclassified with obesity according to new framework

Findings of study on how illegally manufactured fentanyl enters U.S. contradict common assumptions, undermining efforts to control supply

[Press-News.org] Study redefines role of estrogen in cervical cancer