Featured Research

from universities, journals, and other organizations

Single Genetic Locus Linked To Top Cancer-Targeted Biochemical Pathways

Date:
December 4, 1997
Source:
St. Jude Children's Research Hospital
Summary:
While identifying a new cancer-fighting tumor suppressor gene called ARF, scientists at St. Jude Children's Research Hospital have made another, potentially more far-reaching discovery, that a single genetic locus called INK4a encodes protein products that regulate the most frequently targeted biochemical pathways in human cancers, regardless of patient age, tumor site or type.

MEMPHIS, Tenn., November 28, 1997 -- While identifying a new cancer-fighting tumor suppressor gene called ARF, scientists at St. Jude Children's Research Hospital have made another, potentially more far-reaching discovery, that a single genetic locus called INK4a encodes protein products that regulate the most frequently targeted biochemical pathways in human cancers, regardless of patient age, tumor site or type.

Related Articles


The findings, likely to have major implications for the development of anti-cancer therapies, appear in today's issue of Cell.

Pivotal in one of the pathways is the newly identified tumor suppressor ARF. The St. Jude researchers found that ARF interacts with one of the most frequently mutated tumor suppressor genes in human cancer, p53. Tumor suppression by ARF in mice could not occur if p53, which causes cells with defective DNA to arrest their growth and to self-destruct, is itself defective, missing, or otherwise nonfunctional.

The interdepartmental St. Jude research team led by Charles J. Sherr, M.D., Ph.D., an investigator of the Howard Hughes Medical Institute, had earlier found ARF embedded in INK4a. "This economical, overlapping organization of both the ARF and INK4a genes in the same chromosomal location, observed in both mice and humans, is not seen anywhere else in mammals," explained Sherr.

The other cancer-related biochemical pathway, previously discovered, involves a protein separately encoded by INK4a that affects the activity of another tumor suppressor, the retinoblastoma protein, RB.

"What is most surprising," said Sherr, "is that a single genetic locus, INK4a/ARF, encodes two different products that regulate the two biochemical pathways involving p53 and RB." Mutations and deletions that adversely affect the INK4a/ARF locus are very common in different forms of human cancer.

Sherr and his team confirmed ARF as a tumor suppressor by finding that, when ARF is eliminated or knocked-out in mice, the mice develop cancers. At two months of age, mice deprived of ARF began to develop cancer spontaneously and, by six months, a third exhibited malignant tumors. Treating the mice with a known carcinogen or with X-rays hastened the onset of tumors. Conversely, mouse cell lines missing the protein encoded by ARF promptly stopped proliferating when the ARF protein was reintroduced in the cells via a retroviral vector.

Although the exact mechanism by which ARF exerts its antiproliferative effects on cells is unknown, ARF may operate, like p53, through another cell growth inhibitor called p21Cip1 , which is found at increased levels in the presence of ARF.

St. Jude Children's Research Hospital, in Memphis, Tenn, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital's work is primarily supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Single Genetic Locus Linked To Top Cancer-Targeted Biochemical Pathways." ScienceDaily. ScienceDaily, 4 December 1997. <www.sciencedaily.com/releases/1997/12/971204060626.htm>.
St. Jude Children's Research Hospital. (1997, December 4). Single Genetic Locus Linked To Top Cancer-Targeted Biochemical Pathways. ScienceDaily. Retrieved March 3, 2015 from www.sciencedaily.com/releases/1997/12/971204060626.htm
St. Jude Children's Research Hospital. "Single Genetic Locus Linked To Top Cancer-Targeted Biochemical Pathways." ScienceDaily. www.sciencedaily.com/releases/1997/12/971204060626.htm (accessed March 3, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 3, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Treadmill Test Can Predict Chance Of Death Within A Decade

Treadmill Test Can Predict Chance Of Death Within A Decade

Newsy (Mar. 2, 2015) Johns Hopkins researchers analyzed 58,000 heart stress tests to come up with a formula that predicts a person&apos;s chances of dying in the next decade. Video provided by Newsy
Powered by NewsLook.com
Going Gluten-Free Could Get You A Tax Break

Going Gluten-Free Could Get You A Tax Break

Newsy (Mar. 2, 2015) If a doctor advises you to remove gluten from your diet, you could get a tax deduction on the amount you spend on gluten-free foods. Video provided by Newsy
Powered by NewsLook.com
GlaxoSmithKline and Novartis Try Swapping Success

GlaxoSmithKline and Novartis Try Swapping Success

Reuters - Business Video Online (Mar. 2, 2015) GlaxoSmithKline and Novartis have completed a series of asset swaps worth more than $20 billion. As Grace Pascoe reports they say the deal will reshape both drugmakers. Video provided by Reuters
Powered by NewsLook.com
How Can West Africa Rebuild After Ebola?

How Can West Africa Rebuild After Ebola?

Reuters - Business Video Online (Mar. 2, 2015) How best to rebuild the three West African countries struggling with Ebola will be discussed in Brussels this week. As Hayley Platt reports Sierra Leone has the toughest job ahead - its once thriving economy has been ravaged by the disease. Video provided by Reuters
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