Featured Research

from universities, journals, and other organizations

Cancer protein discovery may aid radiation therapy: Blocking cyclin D1 might help sensitize tumors to radiation

Date:
June 9, 2011
Source:
Dana-Farber Cancer Institute
Summary:
Scientists have uncovered a new role for a key cancer protein, cyclin D1, a finding that could pave the way for more-effective radiation treatment of a variety of tumors. They discovered that cyclin D1 can help cancer cells to quickly repair DNA damage caused by radiation treatments, making the tumors resistant to the therapy.

Scientists at Dana-Farber Cancer Institute have uncovered a new role for a key cancer protein, a finding that could pave the way for more-effective radiation treatment of a variety of tumors.

Many cancers are driven in part by elevated levels of cyclin D1, which allow the cells to escape growth controls and proliferate abnormally. In the new research, reported in the June 9 issue of Nature, researchers discovered that cyclin D1 also helps cancer cells to quickly repair DNA damage caused by radiation treatments, making the tumors resistant to the therapy.

Based on this finding, the researchers made cancer cells more sensitive to several cancer drugs and to radiation by using a molecular tool to lower the cancer cells' cyclin D1 levels, said Peter Sicinski, MD, PhD, senior author of the report and a professor of genetics at Dana-Farber.

"This is the first time a cell cycle protein has been shown to be directly involved in DNA repair," said Siwanon Jirawatnotai, PhD, the lead author of the paper. "If we could come up with a strategy to inhibit cyclin D1, it might be very useful in treating a variety of cancers."

The gene for cyclin D1 is the second most-overexpressed gene found in human cancers, including breast cancer, colon cancer, lymphoma, melanoma, and prostate cancer. Cyclin D1's normal function in cellular growth control is to temporarily remove a molecular brake, allowing the cell to manufacture more DNA in preparation for cell division. When cyclin D1 is mutated or is overactivated by external growth signals, the cell may run out of control and proliferate in a malignant fashion.

The findings came in a series of experiments by Jirawatnotai, a post-doctoral fellow in the Sicinski lab. With the goal of uncovering details of cyclin D1's function in human cancer cells, Jirawatnotai broke open four types of cancer cells, isolated the cyclin D1 protein, and searched for other proteins with which it interacted.

The experiment netted more than 132 partner proteins, most of them part of the cell cycle protein mechanism in which cyclin D1 is a major player. But unexpectedly, the scientists also observed that the cyclin D1 protein was binding to a cluster of DNA repair proteins, most importantly RAD51. The RAD51 protein is an enzyme that rushes to broken parts of the cancer cell's DNA instructions and repairs the damage, including damage caused by radiation therapy administered to stop cancer cells' division and growth. In another experiment, it was observed that cyclin D1 was recruited along with RAD51 to the DNA damage site.

"This was a surprise," said Jirawatnotai. "This finding showed that cyclin D1 has an unexpected function in repairing broken DNA." In additional experiments, he used a molecular tool, RNA interference (RNAi) to drastically reduce the level of cyclin D1 in the cancer cells. "When you lower D1 levels, you get poorer repair," he said.

When cancer cells with reduced cyclin D1 protein levels were administered to mice, the resulting tumor proved to be more sensitive to radiation than those grown from cells with overexpressed cyclin D1.

Currently, cyclin D1 is thought to be responsible for driving cancer cell proliferation. Agents that target cyclin D1 are currently in clinical trials, with the goal of reducing cancer cell growth. The new findings strongly suggest that targeting cyclin D1 may increase susceptibility of human cancers to radiation, said the scientists, and this discovery may encourage targeting cyclin D1 even in these cancers whose cells do not depend on cyclin D1 for proliferation.

"Our results potentially change the way we think about cyclin D1 and cancer and may encourage targeting cyclin D1 in a very large pool of human cancers which do not need cyclin D1 for proliferation, but may still depend on cyclin D1 for DNA repair," said Jirawatnotai, who also holds a faculty position at the Mahidol University in Bangkok, Thailand.

In addition to Sicinski and Jirawatnotai, the paper's other authors include Wojciech Michowski, PhD, Yiduo Hu, PhD, Lisa Becks, Yaoyu Wang, PhD, John Quackenbush, PhD, Mick Correll, and David Livingston, MD, Dana-Farber; and Steven Gygi, PhD, Harvard Medical School.

The research was supported by grants from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Dana-Farber Cancer Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Siwanon Jirawatnotai, Yiduo Hu, Wojciech Michowski, Joshua E. Elias, Lisa Becks, Frederic Bienvenu, Agnieszka Zagozdzon, Tapasree Goswami, Yaoyu E. Wang, Alan B. Clark, Thomas A. Kunkel, Tanja van Harn, Bing Xia, Mick Correll, John Quackenbush, David M. Livingston, Steven P. Gygi, Piotr Sicinski. A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers. Nature, 2011; 474 (7350): 230 DOI: 10.1038/nature10155

Cite This Page:

Dana-Farber Cancer Institute. "Cancer protein discovery may aid radiation therapy: Blocking cyclin D1 might help sensitize tumors to radiation." ScienceDaily. ScienceDaily, 9 June 2011. <www.sciencedaily.com/releases/2011/06/110609123344.htm>.
Dana-Farber Cancer Institute. (2011, June 9). Cancer protein discovery may aid radiation therapy: Blocking cyclin D1 might help sensitize tumors to radiation. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2011/06/110609123344.htm
Dana-Farber Cancer Institute. "Cancer protein discovery may aid radiation therapy: Blocking cyclin D1 might help sensitize tumors to radiation." ScienceDaily. www.sciencedaily.com/releases/2011/06/110609123344.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. 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:
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