Navigation Links
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 perce nt 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 togethe r."

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.


'"/>

Source:Thomas Jefferson University


Related biology news :

1. Jefferson Virologists Coax HIV Out of Hiding
2. Jefferson researchers find nanoparticle shows promise in reducing radiation side effects
3. Jefferson biologist coaxing human embryonic stem cells to make dopamine with simpler, faster method
4. Jefferson scientists identify gene defect leading to abnormal skin development and cancer
5. Jefferson researchers building a better rabies vaccine
6. Immune cell communication key to hunting viruses, Jefferson immunologists show
7. Jefferson researchers uncover new way nature turns genes on and off
8. Jefferson scientists find aging gene also protects against prostate cancer development
9. Jefferson scientists find high glucose before surgery raises risk of dangerous complications
10. Jefferson researchers discovery may change thinking on how viruses invade the brain
11. Elderly spinal cord injuries increase five-fold in 30 years, Jefferson neurosurgeons find
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/16/2016)... 16, 2016 The global ... to reach USD 1.83 billion by 2024, according ... Inc. Technological proliferation and increasing demand in commercial ... to drive the market growth.      ... The development of advanced multimodal techniques for biometric ...
(Date:6/9/2016)... 9, 2016 Paris Police ... video security solution to ensure the safety of people and ... during the major tournament Teleste, an international technology ... services, announced today that its video security solution will be ... back up public safety across the country. The system roll-out ...
(Date:6/2/2016)... June 2, 2016 The Department of ... awarded the 44 million US Dollar project, for the ... Plates including Personalization, Enrolment, and IT Infrastructure , ... the production and implementation of Identity Management Solutions. Numerous renowned ... Decatur was selected for the most ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Researchers at the ... commonly-identified miRNAs in people with peritoneal or pleural mesothelioma. Their findings are the subject ... it now. , Diagnostic biomarkers are signposts in the blood, lung fluid or ...
(Date:6/23/2016)... June 23, 2016 A person commits a crime, ... scene to track the criminal down. An outbreak ... and Drug Administration (FDA) uses DNA evidence to track down ... Sound far-fetched? It,s not. The FDA has increasingly used ... investigations of foodborne illnesses. Put as simply as possible, whole ...
(Date:6/23/2016)...   EpiBiome , a precision microbiome engineering company, ... financing from Silicon Valley Bank (SVB). The financing will ... its drug development efforts, as well as purchase additional ... has been an incredible strategic partner to us – ... would provide," said Dr. Aeron Tynes Hammack , ...
Breaking Biology Technology: