Random DNA mix-ups not so random in cancer development

December 3, 2009,

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, .

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 , a 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 /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 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 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.

Source: University of California - San Diego (news : web)

Related Stories

Recommended for you

Experimental arthritis drug prevents stem cell transplant complication

April 24, 2018
An investigational drug in clinical trials for rheumatoid arthritis prevents a common, life-threatening side effect of stem cell transplants, new research from Washington University School of Medicine in St. Louis shows. ...

Scientists develop a new model for glioblastoma using gene-edited organoids

April 24, 2018
Glioblastoma multiforme (GBM) is an incredibly deadly brain cancer and presents a serious black box challenge. It's virtually impossible to observe how these tumors operate in their natural environment and animal models don't ...

Research shows possible new target for immunotherapy for solid tumors

April 24, 2018
Research from the University of Cincinnati (UC) reveals a potential new target to help T cells (white blood cells) infiltrate certain solid tumors.

Changes in breast tissue increase cancer risk for older women

April 24, 2018
Researchers in Norway, Switzerland, and the United States have identified age-related differences in breast tissue that contribute to older women's increased risk of developing breast cancer. The findings, published April ...

Targeting molecules called miR-200s and ADAR2 could prevent tumor metastasis in patients with colorectal cancer

April 24, 2018
Colorectal cancer is the third most common cancer worldwide and the third-leading cause of cancer-related deaths. The main cause of death in patients with colorectal cancer is liver metastasis, with nearly 70% of patients ...

Removing the enablers: Reducing number of tumor-supporting cells to fight neuroblastoma

April 24, 2018
Investigators at the Children's Center for Cancer and Blood Diseases at Children's Hospital Los Angeles provide preclinical evidence that the presence of tumor-associated macrophages—a type of immune cell—can negatively ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.