Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover anti-cancer mechanism that arrests early prostate cancer

04.08.2005


Prostate cancer, the second leading cause of cancer death for men in the United States, is caused by changes in several tummor suppressor genes including PTEN and p53. Up to 70 percent of men with prostate cancer have lost one copy of the PTEN gene at the time of diagnosis, and p53 is absent in a high number of patients with advanced prostate cancer.



Scientists at Memorial Sloan-Kettering Cancer Center have found an unexpected effect of the interaction of these two genes in early stage prostate cancer. In a study published in the August 4 issue of Nature, researchers found that prostate tumor growth is arrested through a biological process called cellular senescence, in which cells stop proliferating and remain alive but fail to respond to normal growth signals.

This research provides some of the first evidence that this phenomenon, normally associated with stress and/or aging, also occurs in cancer both in animal models and in humans. Researchers suggest that drugs that support p53 function could delay progression of prostate cancer in Pten-deficient prostate cancer by triggering cellular senescence.


"In attempting to clarify the role of the Pten and p53 tumor suppressor genes in advanced prostate cancer cells, we unexpectedly discovered that acute loss of Pten results in increased, not decreased p53 function. This works to suppress the further development of cancer," said Pier Paolo Pandolfi, MD, PhD, Head of the Molecular and Developmental Biology Laboratory at Memorial Sloan-Kettering and the study’s senior author. "If we can maintain a higher level of p53 in prostate cancer and induce cellular senescence, the disease should remain stable. This provides new opportunities for therapeutic intervention."

In this experiment, three sets of transgenic mouse models were generated with either the Pten gene, Trp53 gene, or both Pten and Trp53 genes deleted from the prostate. These mice were compared with normal (wild type) mice in the same breeding system. The mice without Pten experienced tumor growth. Those without Trp53 did not. Those with both genes removed had accelerated tumor growth.

Researchers next followed a cohort of 128 mice that were either normal or had the same genetic alterations as described above. All mice had magnetic resonance imaging twice weekly for detection of prostate tumors. While the normal mice and the mice without Trp53 had no tumors at six months, the mice without Pten had small prostate tumors confined to the prostate. The mice without both Pten and Trp53 developed large prostate tumors and died by seven months. This showed that inactivation of Trp53 led to massive tumor growth and lethal prostate cancer only when Pten was depleted or inactivated.

"We realized that the senescence program is intrinsic to all cells, acting as an emergency defense system for prostate cells that are en route to becoming cancerous," explained Zhenbang Chen, PhD, a researcher in Dr. Pier Paolo Pandolfi’s laboratory and the paper’s first author. "As long as the cancer cells remain in the state of cellular senescence, the tipping point to cancer growth will be prevented."

To determine whether their findings were relevant to human prostate cancer, the researchers performed immunohistochemical analysis of prostate tissues. They detected a marker for activation of the senescence pathway when PTEN was inactivated. Next, they examined early stage human prostate cancer sections stained for the senescence marker under high magnification. The senescence marker was seen in area of hyperplasia that may precede the development of carcinoma.

"This study helps us to understand the molecular alterations and mechanisms that can lead to the development of prostate cancer and identifies targets for therapeutic attack," said Dr. Howard Scher, Chief of the Genitourinary Service at Memorial Sloan-Kettering and a co-author of the study. "We are also working to use these models to design more effective clinical tests by determining which combination of agents is most likely to be effective. We are already testing specific drugs to restore PTEN function, based on its role in prostate cancer development and progression."

Joanne Nicholas | EurekAlert!
Further information:
http://www.mskcc.org

More articles from Health and Medicine:

nachricht Second cause of hidden hearing loss identified
20.02.2017 | Michigan Medicine - University of Michigan

nachricht Prospect for more effective treatment of nerve pain
20.02.2017 | Universität Zürich

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>