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 Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>