Featured Research

from universities, journals, and other organizations

Ovarian cancer advances when genes are silenced

Date:
December 14, 2010
Source:
Duke University Medical Center
Summary:
Researchers have found evidence of epigenetics at work on a genome-wide scale in cases of ovarian cancer. One major biological signaling pathway in particular was found to contain many genes influenced by DNA methylation -- a mechanism for turning off genes -- in tumor cells.

There are many mechanisms that alter the activity of genes - direct changes to the DNA code like mutations and deletions, or changes that control when genes are switched on and off, called epigenetic means. Tumor-suppressor genes are often inactivated through epigenetics, which provides an opening for the cancerous growth of cells.

Researchers at the Duke Cancer Institute have found evidence of epigenetics at work on a genome-wide scale in cases of ovarian cancer. One major biological signaling pathway in particular was found to contain many genes influenced by DNA methylation - a mechanism for turning off genes -- in tumor cells.

The researchers performed a series of studies on cancer cell lines and primary tumor specimens from ovarian cancer patients by comparing the genome-wide gene expression profiles of cells that were treated or mock-treated with drugs that inhibit DNA methylation. From these studies they identified 378 candidate methylated genes. From this group, all 43 of the predicted genes the researchers analyzed showed methylation in ovarian cancers.

"We were very surprised to see that so many of these genes were part of one pathway, the TGF-beta signaling pathway, so we conducted studies to further explore how methylation might have an effect on the pathway," said senior author Susan Murphy, Ph.D., assistant professor in the Division of Gynecologic Oncology in Duke OB-GYN and in the Department of Pathology.

When the researchers treated tumor cells with methylation inhibitors, the TGF-beta pathway showed increased activity. This is an important signaling pathway that directs many processes in cells. A smoothly functioning TGF-beta pathway ensures proper cell growth, cell differentiation, and apoptosis (programmed cell death), and helps prevent tumor formation. When this pathway is deregulated, it can instead help tumors grow and metastasize.

The study showed for the first time that TGF-beta pathway function is regulated through methylation. "This is only one piece of a larger puzzle about the biology of ovarian cancer, but we can say that DNA methylation does have an influence on suppressing TGF-beta pathway signaling, which contributes to ovarian cancer."

In addition, the genes they studied included a cluster of genes that strongly correlated with TGF-beta pathway activity in specimens from older women, which suggested that age-related epigenetic changes can accumulate and may contribute to cancer.

Murphy said two different groups of patients the team identified might need different approaches.

"Some women with ovarian cancer have lower expression of these tumor-suppressing genes and may be amenable to epigenetic therapies that lead to gene reactivation - with the caveat that at this point we can't epigenetically reactivate just one gene or a specific group of genes," Murphy said. "Another group of women with ovarian cancer have higher expression of these genes, suggesting it may be possible to specifically inhibit particular components in this pathway to stop tumor development or progression."

The results were published in Genome Research on December 14.

Other authors included co-lead authors Noriomi Matsumura and Zhiqing Huang, Tsukasa Baba and Andrew Berchuck of the Duke Division of Gynecologic Oncology; Seiichi Mori of the Duke Institute for Genome Sciences & Policy; Edwin S. Iversen of the Duke Department of Statistical Sciences; Shingo Fujii of the National Hospital Organization Kyoto Medical Center in Kyoto, Japan; and Ikuo Konishi of the Department of Gynecology and Obstetrics in Kyoto University, Japan.

This work was supported by grants from the Department of Defense CDMRP Ovarian Cancer Research Program and the Japan Society for the Promotion of Science.


Story Source:

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


Journal Reference:

  1. Matsumura N, Huang Z, Mori S, Baba T, Fujii S, Konishi I, Iversen ES, Berchuck A, Murphy SK. Epigenetic suppression of the TGF-beta pathway revealed by transcriptome profiling in ovarian cancer. Genome Research, December 14, 2010 DOI: 10.1101/gr.108803.110

Cite This Page:

Duke University Medical Center. "Ovarian cancer advances when genes are silenced." ScienceDaily. ScienceDaily, 14 December 2010. <www.sciencedaily.com/releases/2010/12/101213181658.htm>.
Duke University Medical Center. (2010, December 14). Ovarian cancer advances when genes are silenced. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2010/12/101213181658.htm
Duke University Medical Center. "Ovarian cancer advances when genes are silenced." ScienceDaily. www.sciencedaily.com/releases/2010/12/101213181658.htm (accessed October 1, 2014).

Share This



More Health & Medicine News

Wednesday, October 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Some Positive Ebola News: Outbreak 'Contained' In Nigeria

Newsy (Sep. 30, 2014) The CDC says a new case of Ebola has not been reported in Nigeria for more than 21 days, leading to hopes the outbreak might be nearing its end. Video provided by Newsy
Powered by NewsLook.com
UN Ebola Mission Head: Immediate Action Is Crucial

UN Ebola Mission Head: Immediate Action Is Crucial

AFP (Sep. 30, 2014) The newly appointed head of the United Nations Mission for Ebola Emergency Response (UNMEER), Anthony Banbury, outlines operations to tackle the virus. Duration: 00:39 Video provided by AFP
Powered by NewsLook.com
CDC Confirms First Case of Ebola in US

CDC Confirms First Case of Ebola in US

AP (Sep. 30, 2014) The CDC has confirmed the first diagnosed case of Ebola in the United States. The patient is being treated at a Dallas hospital after traveling earlier this month from Liberia. (Sept. 30) Video provided by AP
Powered by NewsLook.com
New Breast Cancer Drug Extends Lives In Clinical Trial

New Breast Cancer Drug Extends Lives In Clinical Trial

Newsy (Sep. 30, 2014) In a clinical trial, breast cancer patients lived an average of 15 months longer when they received new drug Perjeta along with Herceptin. 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