Featured Research

from universities, journals, and other organizations

Tumors resistant to radiation therapy may be controlled by the MET oncogene

Date:
April 5, 2011
Source:
Journal of the National Cancer Institute
Summary:
Ionizing radiation treats many cancers effectively, but in some patients a few tumor cells become resistant to radiation and go on to cause relapse and metastasis. A growth factor-receptor protein called MET may be a key player in these cells' resistance to radiation, and drugs targeting MET may help to prevent radiation-induced metastasis, according to a new study.

Ionizing radiation treats many cancers effectively, but in some patients a few tumor cells become resistant to radiation and go on to cause relapse and metastasis. A growth factor-receptor protein called MET may be a key player in these cells' resistance to radiation, and drugs targeting MET may help to prevent radiation-induced metastasis, according to a study published online April 4th in the Journal of the National Cancer Institute.

The gene that encodes MET is known as a cancer-promoting gene, or oncogene. It is expressed at high levels in many cancers and is associated with metastasis. But the exact role it plays and how it may induce radiation-resistant tumor cells is unclear.

To explore the molecular mechanisms behind radioresistance, the group led by Carla Boccaccio, M.D. and Paolo M. Comoglio, M.D., of the Institute for Cancer Research at Candiolo, University of Turin Medical School, examined the expression of the MET gene and the activity of the MET protein in human cancer cell lines before and after exposure to ionizing radiation. They also observed the effect of radiation on two proteins that regulate MET--ataxia telangiectasia mutated (ATM) and nuclear factor kappa B or NF-κB.

They found that after radiation treatment, MET expression increased up to fivefold due to activation of ATM and NF-κB. The tumor cells that survived irradiation became more invasive than previously. Moreover, inhibiting MET counteracted this increased invasiveness and promoted death of the tumor cells (apoptosis). In mice, treatment with MET inhibitors, such as specific small-molecule kinase inhibitors, enhanced the effect of radiation, stopping growth or inducing shrinkage of tumors.

The authors conclude that ionizing radiation drives overexpression and activity of MET through the ATM and NF-κB signaling pathways, making some tumor cells resistant to radiation and more invasive. They also conclude that drugs that inhibit MET might counter radiation resistance.

"This has important therapeutic implications," they write, "as it suggests that the combination of radiotherapy with MET inhibition can radiosensitize cancer cells."

In an accompanying editorial, Olga Guryanova M.D., Ph.D. and Shideng Bao, Ph.D., of the Lerner Research Institute at the Cleveland Clinic, Cleveland, Ohio, note that the study adds new details to emerging knowledge of the roles of MET and NF-κB in therapeutic resistance. "The finding that NF-κB activation is ATM dependent adds yet another vignette to the picture," they write.

The editorialists point out that the study also raises questions for future investigation. One step, they suggest, would be to test human tumor cells isolated from surgical specimens to confirm the results. Another would be to determine whether MET expression is elevated in cancer stem cells, which have shown resistance to radiation and chemotherapy in some studies.

"Augmenting the sensitivity of resistant cancer cells to conventional treatments has been the subject of great effort," they write. "Improved radiotherapy with radiosensitizers is expected to increase the efficacy of cancer treatment."


Story Source:

The above story is based on materials provided by Journal of the National Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Francesca De Bacco, Paolo Luraghi, Enzo Medico, Gigliola Reato, Flavia Girolami, Timothy Perera, Pietro Gabriele, Paolo M. Comoglio, Carla Boccaccio. Induction of MET by Ionizing Radiation and Its Role in Radioresistance and Invasive Growth of Cancer. Journal of the National Cancer Institute, 2011; DOI: 10.1093/jnci/djr093

Cite This Page:

Journal of the National Cancer Institute. "Tumors resistant to radiation therapy may be controlled by the MET oncogene." ScienceDaily. ScienceDaily, 5 April 2011. <www.sciencedaily.com/releases/2011/04/110404161704.htm>.
Journal of the National Cancer Institute. (2011, April 5). Tumors resistant to radiation therapy may be controlled by the MET oncogene. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2011/04/110404161704.htm
Journal of the National Cancer Institute. "Tumors resistant to radiation therapy may be controlled by the MET oncogene." ScienceDaily. www.sciencedaily.com/releases/2011/04/110404161704.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) — A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Do More Wedding Guests Make A Happier Marriage?

Do More Wedding Guests Make A Happier Marriage?

Newsy (Aug. 20, 2014) — A new study found couples who had at least 150 guests at their weddings were more likely to report being happy in their marriages. Video provided by Newsy
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) — Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 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:
from the past week

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