Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find BRCA1 tumor suppression nullified by cyclin D1

08.08.2005


Study results reaffirm cyclin D1 as a candidate target for molecular therapeutic control of breast tumor development.



For about a decade, scientists have recognized that many cases of hereditary breast cancer result from a mutation of a specific gene called BRCA1, which, in its normal state, helps keep tumor formation in check. About five to 10 percent of breast cancer cases arise from these genetic miscues, about half of which are linked to the abnormal functioning of BRCA1.

But now scientists have discovered that a protein called cyclin D1, grossly overproduced in about half of all cases of breast cancer, can also disrupt BRCA1’s normal role as a cancer inhibitor. They found that because cyclin D1 binds to the same estrogen receptor as does BRCA1, when the cell is flooded with cyclin D1, BRCA1 is unable to activate a pathway that stops cancer development.


The results reaffirm cyclin D1 as a candidate target for molecular therapeutic control of breast tumor development.

"We’ve previously shown that if you have a gene therapy vector that blocks cyclin D1 in breast tumors, you can block the growth of those tumors," said Richard Pestell, M.D., Ph.D., director of the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center and senior author of the paper published in the August 1 issue of Cancer Research.

Also part of the Georgetown University research team were Chenguang Wang, Ph.D., assistant professor at the Lombardi Comprehensive Cancer Center and the lead author of the article, and Georgetown Professor of Oncology Eliot M. Rosen, a co-investigator on the study, which was funded in part by a grant from the Department of Defense. Participating in the research from the Georgetown oncology department were Saijun Fan, Zhiping Li, Maofu Fu, Mahadev Rao, Yongxian Ma, and Chris Albanese.

This paper, Pestell said, identifies the mechanism by which cyclin D1 nullifies one activity of the tumor suppressor BRCA1.

"Cyclin D1 is a collaborative oncogene and is sufficient for the induction of breast tumorogenesis in transgenic mice," he said. "This protein blocks the functional activity of the BRCA1 tumor suppressor. The science reported in this paper describes an important oncogene/tumor suppressor interaction."

The tumor-promoting action of various oncogenic sources upregulating expression of cyclin D1 converge at the common binding site on the estrogen receptor alpha (ERa) that is shared by both cyclin D1 and BRCA1. This research builds on a major discovery by the laboratory by Dr. Rosen, showing that BRCA1 interacts with, and inhibits the activity of ERa, the protein that transduces the growth signal of estrogen.

"This may help explain why the cyclin D1 gene and the BRCA1 gene are important primarily in hormone responsive cancers," Pestell said. "The interaction occurs at the level of the ERa hormone receptor."

Cyclin D1 is a protein produced by cells and routinely functions in events that promote cell division. In cancer, cyclin D1 is regulated and abundantly overexpressed by a number of factors that promote tumor growth, such as the oncogenes ErB2, src, and ras. In more than half of human patients with breast cancer, tumor cells produce as much as eight times the amount of cyclin D than healthy breast cells.

Cyclin D1 interferes with BRCA1 function because the two proteins both bind to the same spot on ERa, an important protein that governs cell proliferation properties in both healthy and cancerous cells. In healthy cells, BRCA1 binds to ERa to restrain and control estrogen-target genes that promote cell division. In cancer cells, however, cyclin D1 occupies the binding site on the ERa to promote proliferation. The abundance of cyclin D1 pre-empts BRCA1 binding to the estrogen receptor and negates the tumor suppressor role of the BRCA1 gene product.

In addition to their Georgetown research colleagues, Wang and Pestell conducted their research in concert with Michael Lisanti, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, N.Y.; Benita Katzenellenbogen, Departments of Molecular and Integrative Physiology and Cell and Structural Biology, University of Illinois and College of Medicine, Urbana, Ill.; Peter J. Kushner, Metabolic Research Unit, University of California-San Francisco School of Medicine, San Francisco, Calif.; and Barbara Weber, Department of Molecular Genetics, University of Pennsylvania, Philadelphia, Pa.

Laura Cavender | EurekAlert!
Further information:
http://www.georgetown.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>