Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson Scientists Identify Gene Mutation Potentially Involved in Breast Cancer Initiation

02.06.2006
Jefferson Scientists Identify Gene Mutation Potentially Involved in Breast Cancer Initiation

Researchers at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia and at the Albert Einstein College of Medicine in New York have found evidence suggesting that a mutation in a gene that normally helps block the formation of breast tumors could play a role in the initiation of a major form of breast cancer.

The team, led by cell biologist Michael P. Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College and Richard Pestell, M.D., Ph.D., director of Jefferson’s Kimmel Cancer Center, found that a known mutation in the Caveolin-1 gene is present in approximately 19 percent of all breast cancers that are fed by estrogen – so called “estrogen receptor-positive” cells. The group also discovered six new Caveolin-1 mutations associated with estrogen-driven breast cancers. As many as nearly 35 percent of such breast cancers may carry Caveolin-1 mutations, Dr. Lisanti says. Caveolin proteins, which play important roles in cell communication, are also involved in a number of diseases and conditions, such as cancer, atherosclerosis, diabetes, Alzheimer’s disease and muscular dystrophy.

The researchers, reporting in June 2006 in the American Journal of Pathology, say their results open up the possibility that Caveolin-1 mutations may be involved in the development of estrogen-positive human breast cancer, which accounts for some 70 percent of all breast cancers.

“This is the first demonstration that a specific Caveolin-1 mutation is exclusively connected to being estrogen-receptor positive,” says Dr. Lisanti, noting that in tests of breast tumor samples, none of those that were estrogen-receptor negative showed caveolin mutations.

“One-third of estrogen receptor-positive patients actually had caveolin mutations, making it one of the most common mutations in that population,” he says. “Usually about 70 percent of all human breast cancers are estrogen receptor-positive and 30 percent are negative. That’s one-third of the major form of human breast cancer.”

Dr. Lisanti explains that he and his colleagues had wanted to test the hypothesis that the loss of a functioning Caveolin-1 gene could increase the activity, or “upregulate” the expression of estrogen receptors. Only 5 to 10 percent of the cells in the normal human breast express estrogen receptors, yet the receptor activity for some reason rises dramatically in premalignant lesions and cancer.

Dr. Lisanti’s team developed mice lacking the Caveolin-1 gene and found a dramatic increase in both number and activity of estrogen-positive receptors in mouse breast tissue, specifically in breast epithelial cells, in turn, promoting cell growth. Caveolin-1, Dr. Lisanti suggests, could act as a kind of “switch” that regulates receptor activity and cell proliferation.

“It is the first time that we can say that the loss of function of caveolin gene expression plays a role in the specific upregulation of estrogen receptor,” he says. “It helps explain the nature of this transition from nonmalignant to malignant tissue.”

Dr. Lisanti explains that estrogen receptors are thought to help turn on certain genes such as cyclin D1, which in turn promote cancer development. “We’ve elicited a new pathway for mammary tumorigenesis,” he says. “Before, we could say that estrogen receptors turned on cyclin D1, which was enough to cause mammary tumorigenesis. Now we’ve added another link: inactivation of caveolin as the first initiation step.”

The team found that cyclin D1 activity in human breast cancer samples was increased, specifically after estrogen treatment. “In essence, we have created a preclinical model in which to study the role of estrogen and caveolin deficiency in breast cancer development,” he says. “It’s a new signaling pathway for understanding the pathogenesis of human breast cancer with caveolin gene inactivation as the initiating step. It all fits together.”

The group subsequently showed in laboratory studies that in mouse mammary cells lacking caveolin and certain growth-stimulating factors, estrogen receptors were again increased, leading them to conclude that two factors may be required for estrogen receptor upregulation: Caveolin gene inactivation and growth factor depletion.

The findings may have clinical implications. According to Dr. Lisanti, those breast cancer patients who are estrogen receptor-positive and who have caveolin mutations are much more likely to have a cancer recur than are such individuals who don’t carry caveolin gene mutations. “It’s a risk factor,” he notes.

Steve Benowitz | EurekAlert!
Further information:
http://www.jefferson.edu

More articles from Life Sciences:

nachricht A novel synthetic antibody enables conditional “protein knockdown” in vertebrates
20.08.2018 | Technische Universität Dresden

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

There are currently great hopes for solid-state batteries. They contain no liquid parts that could leak or catch fire. For this reason, they do not require cooling and are considered to be much safer, more reliable, and longer lasting than traditional lithium-ion batteries. Jülich scientists have now introduced a new concept that allows currents up to ten times greater during charging and discharging than previously described in the literature. The improvement was achieved by a “clever” choice of materials with a focus on consistently good compatibility. All components were made from phosphate compounds, which are well matched both chemically and mechanically.

The low current is considered one of the biggest hurdles in the development of solid-state batteries. It is the reason why the batteries take a relatively long...

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

A novel synthetic antibody enables conditional “protein knockdown” in vertebrates

20.08.2018 | Life Sciences

Metamolds: Molding a mold

20.08.2018 | Information Technology

It’s All in the Mix: Jülich Researchers are Developing Fast-Charging Solid-State Batteries

20.08.2018 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>