Featured Research

from universities, journals, and other organizations

Random DNA mix-ups not so random in cancer development

Date:
December 3, 2009
Source:
University of California - San Diego
Summary:
Researchers have pinpointed a mechanism that may help explain how chromosomal translocations -- the supposedly random shuffling of large chunks of DNA that frequently lead to cancer -- aren't so random after all. They have developed a model of such chromosomal mix-ups in prostate cancer which indicates that the male sex hormone (androgen) receptor unexpectedly plays a key role in driving specific translocations in the development of cancer.

Researchers at the UC San Diego School of Medicine have pinpointed a mechanism that may help explain how chromosomal translocations -- the supposedly random shuffling of large chunks of DNA that frequently lead to cancer -- aren't so random after all. They have developed a model of such chromosomal mix-ups in prostate cancer which indicates that the male sex hormone (androgen) receptor unexpectedly plays a key role in driving specific translocations in the development of cancer.

A better understanding of the origin and behavior of such translocations may ultimately lead to ways to both predict and perhaps interfere with their formation, and in turn, cancer development.

Chunru (Ruth) Lin, Liuqing (Luke) Yang and Michael G. Rosenfeld, MD, Howard Hughes Medical Institute investigator and Professor of Medicine at the UC San Diego School of Medicine, headed the basic research study, to be published on line December 3, 2009 in advance of publication in the journal Cell.

A series of studies showed that, under certain conditions involving some sort of genetic "stress" -- such as cigarette smoke, a toxic chemical exposure or radiation -- the androgen receptor can act in concert with several key enzymes and pathways induced by genotoxic stress to unexpectedly direct specific translocations leading to cancer.

"In the future, one goal would be to find tumor-causing translocations in breast and other cancers and develop a chemical library screen to find compounds that might inhibit these events in cancer formation/behavior," said Rosenfeld.

According to Rosenfeld, chromosome mix-ups are a hallmark of leukemias and lymphomas and, increasingly, other cancers such as more aggressive forms of prostate cancer. Scientists have known that various types of genetic stress can lead to random breaks in DNA and rearrangements in chromosomes, resulting in excessive cell growth and cancer, but the exact mechanisms have been poorly understood.

Evidence from other research teams pointed to the important role of the androgen receptor in the development of translocations in more aggressive forms of prostate cancer. The UC San Diego research team created a tumor translocation model in prostate cancer and found that instead of random DNA breaks, the breaks were in specific chromosomal areas bound by the androgen receptor which directed the pattern of cancer-causing translocations.

Rosenfeld's group identified several mechanisms, some involving specific enzymatic pathways that worked together with the androgen receptor to form specific translocations.

"Our findings suggest that sex steroid receptors -- androgen and estrogen receptors -- can cause mutations when in the presence of genotoxic stress, and form site-specific chromosomal translocations," Rosenfeld said.

He noted that understanding the molecular mechanisms that underlie tumor translocations and the specific strategies used by normal cells to protect against such rearrangements could provide insights into cancer development and eventually help in the development of new therapeutic approaches.

Additional contributors include co-first authors Chunru Lin and Liuqing Yang, Bogdan Tanasa, Kenny Ohgi and Jie Zhang of the Howard Hughes Medical Institute (HHMI); Bong-gun Ju, HHMI and Sogang University, Seoul; Kasey Hutt, UCSD Bioinformatics Graduate Program; Dave Rose, UCSD Department of Medicine, Division of Endocrinology and Metabolism; and Xiang-Dong Fu and Christopher K. Glass, UCSD Department of Cellular and Molecular Medicine.

This study was funded in part by grants from The National Institutes of Health/National Cancer Institute, the Department of Defense and the Prostate Cancer Foundation.


Story Source:

The above story is based on materials provided by University of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University of California - San Diego. "Random DNA mix-ups not so random in cancer development." ScienceDaily. ScienceDaily, 3 December 2009. <www.sciencedaily.com/releases/2009/12/091203132146.htm>.
University of California - San Diego. (2009, December 3). Random DNA mix-ups not so random in cancer development. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2009/12/091203132146.htm
University of California - San Diego. "Random DNA mix-ups not so random in cancer development." ScienceDaily. www.sciencedaily.com/releases/2009/12/091203132146.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. 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