Featured Research

from universities, journals, and other organizations

Well-known cancer gene NRAS produces 5 variants, study finds

Date:
April 7, 2014
Source:
Ohio State University Wexner Medical Center
Summary:
The NRAS gene, known to play a fundamental role in cancer development, produces five gene variants, or isoforms, rather than just one form, as thought, new research shows. The study identified four previously unknown variants that the NRAS gene produces. The finding might help improve drugs for cancers in which NRAS plays a crucial role. It also suggests that NRAS might affect additional target molecules in cells.

A new study shows that a gene discovered 30 years ago and now known to play a fundamental role in cancer development produces five different gene variants (called isoforms), rather than just the one original form, as thought.

The study of the NRAS gene by researchers at The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) identified four previously unknown variants that the NRAS gene produces.

The finding might help improve drugs for cancers in which aberrant activation of NRAS plays a crucial role. It also suggests that NRAS might affect additional target molecules in cells, the researchers say.

The isoforms show striking differences in size, abundance and effects. For example, the historically known protein (isoform 1) is 189 amino-acids long, while one of the newly discovered variants, isoform 5, is only 20 amino-acids long.

The study is published in the Proceedings of the National Academy of Sciences.

"We believe that the existence of these isoforms may be one reason why NRAS inhibitors have so far been unsuccessful," says corresponding author Albert de la Chapelle, MD, PhD, professor of Medicine and the Leonard J. Immke Jr. and Charlotte L. Immke Chair in Cancer Research.

Co-senior author Clara D. Bloomfield, MD, Distinguished University Professor and Ohio State University Cancer Scholar, notes that one of the newly discovered isoforms might play a greater role in the development of some cancers than the known protein itself.

"Targeting the NRAS pathway may have been unsuccessful in the past because we were unaware of the existence of additional targets of these novel isoforms," says Bloomfield, who is also senior adviser to the OSUCCC -- James and holds the William Greenville Pace III Endowed Chair in Cancer Research.

"The discovery of these isoforms might open a new chapter in the study of NRAS," says first author Ann-Kathrin Eisfeld, MD, a postdoctoral fellow in the laboratories of de la Chapelle and of Bloomfield. "Knowing that these isoforms exist may lead to the development of drugs that specifically decrease or increase the expression of one of them and provide more effective treatment for cancer patients."

For this study, de la Chapelle, Eisfeld and their colleagues analyzed expression of the NRAS isoforms in a variety of normal and matched tumor samples. Key technical findings include:

  • The isoforms showed modest but significant differences in expression in normal and malignant samples;
  • Each isoform had different effects on NRAS target molecules;
  • Isoform 5 was the most aggressive variant in proliferation and transformation assays;
  • Isoforms 3 and 5, the smallest of the isoforms (40 and 20 amino acids respectively), were found in both the cell nucleus and cytoplasm.

Story Source:

The above story is based on materials provided by Ohio State University Wexner Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. A.-K. Eisfeld, S. Schwind, K. W. Hoag, C. J. Walker, S. Liyanarachchi, R. Patel, X. Huang, J. Markowitz, W. Duan, G. A. Otterson, W. E. Carson, G. Marcucci, C. D. Bloomfield, A. de la Chapelle. NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation. Proceedings of the National Academy of Sciences, 2014; 111 (11): 4179 DOI: 10.1073/pnas.1401727111

Cite This Page:

Ohio State University Wexner Medical Center. "Well-known cancer gene NRAS produces 5 variants, study finds." ScienceDaily. ScienceDaily, 7 April 2014. <www.sciencedaily.com/releases/2014/04/140407143717.htm>.
Ohio State University Wexner Medical Center. (2014, April 7). Well-known cancer gene NRAS produces 5 variants, study finds. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/04/140407143717.htm
Ohio State University Wexner Medical Center. "Well-known cancer gene NRAS produces 5 variants, study finds." ScienceDaily. www.sciencedaily.com/releases/2014/04/140407143717.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
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