Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Normal gene hinders breast cancer chemotherapy

12.06.2012
Mutated tumor suppressor gene p53 leads to better results

Presence of normal p53, a tumor suppressor gene, instead of a mutated version, makes breast cancer chemotherapy with doxorubicin less effective. The preclinical study led by MD Anderson scientists was published today in the journal Cancer Cell.

The research, which challenges the existing paradigm, is another step closer to personalized cancer medicine for breast cancer.

"It's really important to understand the genetic defects a tumor cell has before we treat it," said lead author Guillermina Lozano, Ph.D., professor and chair of the Department of Genetics. "What we learned here is the complete opposite of what we expected. We thought tumors would respond better to treatment if the p53 gene were normal. But the opposite was true, and for a really interesting reason."

Lozano said the research in mouse models showed that non-mutated p53 halted cell division, initiating a senescence (cell aging) process that allowed cells to survive. These senescent cells produce factors that stimulate adjacent cells to grow, fueling the relapse. Mutant p53 cells do not arrest and proceed through the cell cycle into cell division with broken chromosomes caused by the chemotherapy.

"That's a signal for the cell to die," she said. "It can't go any farther."

P53 status crucial to predicting response

The tumor suppressor p53 is mutated or inactivated in the majority of cancers, and about one-third of breast cancers have mutations in the gene. It has long been thought that normal p53 results in a better chemotherapy response, but the evidence in breast cancer has been conflicting.

According to the National Cancer Institute, about 227,000 women in the United States are diagnosed with breast cancer each year.

In this study, doxorubicin-treated p53 mutant tumor cells did not stop cell proliferation, leading to abnormal mitoses and cell death, whereas tumors with normal p53 arrested, avoiding mitotic catastrophe.

"There are a lot of data out there on responses of women to doxorubicin and other drugs that break DNA," Lozano said. "The response rates were mixed, and we never understood the difference. Now we understand that we need to know the p53 status to predict a response."

Results consistent in mouse, human models

The scientists first examined the response to doxorubicin in mice with mammary tumors and the role of p53 in the chemotherapy process. When they analyzed the results, they found the mice that responded poorly to treatment had normal p53 genes, while the mice that responded best had mutated p53 genes.

Using human breast tumor cell lines with normal p53, the researchers then replicated the mouse experiment with the same results. When the cells were treated with doxorubicin, which is known commercially as Adriamycin®, they basically stopped. When the p53 gene was removed, the cells continued through the cell cycle and eventual destruction.

Future research to examine relapse

Lozano said the next piece of the research puzzle involves looking at what happens after breast cancer has been treated successfully but comes back.

"A lot of breast cancer tumors relapse," she said. "We want to find out what additional changes these cells acquire that allow them to bypass the cell death mechanism."

In addition to Lozano, the team included MD Anderson researchers James Jackson, Ph.D., Vinod Pant, Ph.D., Leslie Chang, Daniel Garza and Peirong Yang M.S., Department of Genetics; Qin Li M.S., Department of Genetics and The University of Texas Graduate School of Biomedical Sciences Program in Genes and Development, Houston; Alfonso Quintas-Cardama, M.D., and Taghi Manshouri, Ph.D., Department of Leukemia; Omid Tavana, Ph.D. Department of Immunology; Adel El-Naggar, MD., Ph.D., Department of Pathology; and Yi Li, Ph.D., Lester and Sue Smith Breast Center and Department of Molecular and Cell Biology, Baylor College of Medicine, Houston.

This project was funded by grants from the National Cancer Institute and the National Institutes of Health, a Theodore N. Law Endowment for Scientific Achievement and a Dodie P. Hawn Fellowship in Cancer Genetics Research.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For eight of the past 10 years, including 2011, MD Anderson has ranked No. 1 in cancer care in the "Best Hospitals" survey published annually in U.S. News & World Report.

Scott Merville | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
21.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Nagoya physicists resolve long-standing mystery of structure-less transition

21.08.2017 | Materials Sciences

Chronic stress induces fatal organ dysfunctions via a new neural circuit

21.08.2017 | Health and Medicine

Scientists from the MSU studied new liquid-crystalline photochrom

21.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>