Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sporadic breast cancers start with ineffective DNA repair systems

30.11.2010
Breast cancers that arise sporadically, rather than through inheritance of certain genes, likely start with defects of DNA repair mechanisms that allow environmentally triggered mutations to accumulate, according to researchers at the University of Pittsburgh School of Medicine, Magee-Womens Hospital of UPMC and the University of Pittsburgh Cancer Institute.

The findings, reported this week in the early online edition of the Proceedings of the National Academy of Sciences, indicate that potent chemotherapy drugs that target DNA in later-stage cancers could be an effective way to treat the earliest of breast tumors.

Recent research has focused on familial breast cancers, in part because the predisposing genes have been well-characterized and women at risk can be identified, said Jean J. Latimer, Ph.D., assistant professor of obstetrics, gynecology and reproductive sciences at Pitt's School of Medicine. But these cases only comprise 15 percent of the 190,000 breast cancers that are diagnosed every year.

Research on sporadic breast cancer has involved the use of available cell lines derived from late-stage tumors, but most newly diagnosed tumors in the U.S. are stage I, the earliest form of invasive disease.

"Our team is able to grow stage I breast cancer cells – before they have spread to adjacent tissues and lymph nodes – allowing us to examine the mechanisms that underlie cancer development in people who didn't inherit a faulty gene," Dr. Latimer said. "The advent of innovative tissue engineering techniques has finally made it possible for us to culture these cells to determine what has gone wrong."

In earlier work, she and her colleagues found that breast tissue does not repair everyday damage to DNA as well as other tissues, such as skin. Ultraviolet light, for example, can cause mutations, but a sophisticated system of nucleotide excision repair (NER) proteins trolls the DNA strands to identify problems and initiate repair processes. The same system repairs damage caused by many environmental carcinogens, including tobacco smoke.

"Even in healthy breast tissue, this system is only about one-fifth as effective as it is in skin," Dr. Latimer noted. "This deficiency could set the stage for sporadic cancer development, with the risk increasing with age as DNA damage accumulates."

For the study, the researchers grew and assessed 19 sporadic, stage I breast tumors placed into culture directly from surgeries to test their NER pathways. In every case, there was a deficiency in repair capacity compared to disease-free breast tissue.

"That is a remarkably consistent feature for cancers that might otherwise seem random in their genesis," Dr. Latimer noted. "We rarely see a universal rule when it comes to breast cancer, but then until now, we have rarely studied stage I disease."

Some chemotherapy drugs work especially well on cells that exhibit reduced DNA repair, but they are typically given in later-stage disease. The new findings suggest, however, that these approaches could be effective in treating early stage disease, she noted.

Co-authors include Jennifer M. Johnson, M.D., Ph.D., Crystal M. Kelly, M.D., Ph.D., Tiffany D. Miles, Ph.D., Kelly A. Beaudrey-Rodgers, M.S., Nancy A. Lalanne, B.S., Victor G. Vogel, M.D., Amal Kanbour-Shakir, M.D., Joseph L. Kelley, M.D., Ronald R. Johnson, M.D., and Stephen G. Grant, Ph.D., all of the University of Pittsburgh.

The research was funded by the National Institutes of Health, the U.S. Department of Defense, the Pennsylvania Department of Health, the Komen for the Cure Awards, and the American Cancer Society.

Anita Srikameswaran | EurekAlert!
Further information:
http://www.upmc.edu

More articles from Life Sciences:

nachricht 'Lipid asymmetry' plays key role in activating immune cells
20.02.2018 | Biophysical Society

nachricht New printing technique uses cells and molecules to recreate biological structures
20.02.2018 | Queen Mary University of London

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

'Lipid asymmetry' plays key role in activating immune cells

20.02.2018 | Life Sciences

MRI technique differentiates benign breast lesions from malignancies

20.02.2018 | Medical Engineering

Major discovery in controlling quantum states of single atoms

20.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>