Featured Research

from universities, journals, and other organizations

New pathway found for regulation of blood vessel growth in cancer

Date:
March 1, 2012
Source:
Emory University
Summary:
Researchers have identified a new function for a gene that normally prevents the development of cancer. Scientists had known that the gene, which encodes a protein called p14 ARF, works inside the cell to control proliferation and division. A team has discovered that p14 ARF also regulates tumor-induced angiogenesis, the process by which growing cancers attract new blood vessels.

Blood vessels are attracted toward a cell pellet (P). Scientists have discovered that ARF, known to act inside the cell, can also inhibit the ability of a tumor to attract new blood vessels.
Credit: Image courtesy of Emory University

Researchers at Winship Cancer Institute have identified a new function for a gene that normally prevents the development of cancer.

Related Articles


Scientists had known that the gene, which encodes a protein called p14 ARF, works inside the cell to control proliferation and division. A team led by Erwin Van Meir, PhD, discovered that p14 ARF also regulates tumor-induced angiogenesis, the process by which growing cancers attract new blood vessels.

The findings, published in the Journal of Clinical Investigation, provide insight into how cancers form and progress, communicate with surrounding vascular cells and could guide the development of new therapies to fight tumors whose growth is driven by loss of p14 ARF.

Van Meir is professor of neurosurgery and hematology & medical oncology at Emory University School of Medicine, and director of the Laboratory for Molecular Neuro-Oncology at Winship Cancer Institute. Abdessamad Zerrouqi, PhD, research associate, is the first author of the paper.

Pinning down the new function for p14 ARF was a several-year detective investigation for Zerrouqi. The gene was a slippery target because growing cells in culture tend to lose or silence it, he says. P14 ARF is not turned on in most tissues of the body, but is activated in response to aberrant growth signals.

The gene encoding p14 ARF is mutated or silenced in many types of cancers, including most gliomas, the most common brain cancer in adults. People who inherit mutations affecting this gene develop "melanoma-astrocytoma syndrome," with increased occurrence of both types of tumors. ARF stands for "alternate reading frame" because the DNA sequence overlaps with another protein that is read out of step in comparison to ARF. Previous research had linked the function of p14 ARF to another gene, p53, which is also frequently mutated in cancers. P53 is known as "guardian of the genome" because it shuts down cell division in response to DNA damage.

Zerrouqi says several clues pointed to a separate function for p14 ARF. P14 ARF is often lost when astrocytoma progresses to glioblastoma, a more deadly form of brain cancer.

"These tumors are bigger, more infiltrative and more vascularized," he says. "Yet p53 is usually lost at an early stage, before this transition takes place. This suggested that p14 ARF has a function that is independent of p53."

Zerrouqi could show that restoring p14 ARF in cells from a tumor that had lost it interfered with the tumor's ability to stimulate blood vessel growth. P14 ARF induces brain cancer cells to secrete a protein called TIMP3, which inhibits vascular cell migration, he found.

Zerrouqi and Van Meir's findings are applicable to brain cancers as well as several other cancer types. TIMP3 itself has been found to be silenced in brain, kidney, colon, breast and lung cancers, suggesting that it is an obstacle to their growth.

The research was supported by the National Cancer Institute, the Pediatric Brain Tumor Foundation of the US, the American Brain Tumor Association, and the Southeastern Brain Tumor Foundation.

Zerrouqi, postdoc Beata Pyrzynska and Van Meir collaborated with Maria Febbraio, PhD, a researcher at the Cleveland Clinic to probe angiogenesis and Daniel J. Brat, MD, PhD, Emory professor of pathology and laboratory medicine, for pathological expertise.


Story Source:

The above story is based on materials provided by Emory University. The original article was written by Quinn Eastman. Note: Materials may be edited for content and length.


Journal Reference:

  1. Abdessamad Zerrouqi, Beata Pyrzynska, Maria Febbraio, Daniel J. Brat, Erwin G. Van Meir. P14ARF inhibits human glioblastoma–induced angiogenesis by upregulating the expression of TIMP3. Journal of Clinical Investigation, 2012; DOI: 10.1172/JCI38596

Cite This Page:

Emory University. "New pathway found for regulation of blood vessel growth in cancer." ScienceDaily. ScienceDaily, 1 March 2012. <www.sciencedaily.com/releases/2012/03/120301143801.htm>.
Emory University. (2012, March 1). New pathway found for regulation of blood vessel growth in cancer. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2012/03/120301143801.htm
Emory University. "New pathway found for regulation of blood vessel growth in cancer." ScienceDaily. www.sciencedaily.com/releases/2012/03/120301143801.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins