Navigation Links
Protein and microRNA block cellular transition vital to metastasis
Date:2/25/2011

HOUSTON - Like a bounty hunter returning escapees to custody, a cancer-fighting gene converts organ cells that change into highly mobile stem cells back to their original, stationary state, researchers report online at Nature Cell Biology.

This newly discovered activity of the p53 gene offers a potential avenue of attack on breast cancer stem cells thought to play a central role in progression and spread of the disease, according to scientists at The University of Texas MD Anderson Cancer Center.

Long known for monitoring DNA damage and forcing defective cells to kill themselves, p53 also activates bits of RNA that block two proteins, the researchers found. This prevents conversion of epithelial-differentiated cells, which line or cover an organ, into cells that resemble mesenchymal stem cells when stimulated by the TGF-??growth factor.

Mesenchymal cells are mobile adult stem cells that can reproduce themselves and differentiate into a variety of cell types

"Blocking this conversion from epithelial cell to a mesenchymal cell type is important because that change plays an essential role in cancer metastasis," said senior author Mien-Chie Hung, Ph.D., professor and chair of MD Anderson's Department of Molecular and Cellular Oncology.

Cancer treatment potential

"We found that p53 activates the micro RNA miR-200c, which forces cells that have taken on stem cell traits to revert to epithelial form," Hung said. "Activating this pathway has therapeutic potential to target tumor-initiating cells that have stem cell characteristics."

Research has shown that about 80 percent of all solid tumors begin in the epithelial cells. However, 90 percent of cancer deaths are caused by metastasis, the progression and spread of the disease to other organs.

The epithelial-to-mesenchymal transition (EMT) and its opposite process play important roles in embryonic development. Research has connected EMT activation to cancer progression and metastasis. Recent studies tie EMT to gain of stem cell traits in normal and transformed cells.

Cell status depends on p53, miR-200c levels

A series of experiments established that the p53 protein activates the miR-200c gene to produce the microRNA and that expression of the protein and miR-200c moved up and down together.

  • Knockout experiments in normal breast epithelial cells consistently showed that p53 expression stifled the EMT transition.

  • Cells with reduced p53 changed into mesenchymal-like cells.

  • When miR-200c was overexpressed in cells with low levels of p53, the cells took on epithelial characteristics, indicating that p53 uses the microRNA to block or reverse the transition to mesenchymal-type cells.

  • Mutated p53 failed to produce miR-200c, increasing stem cells in the cell culture.

  • Tissue array analysis of gene expression in 106 human breast tumor samples showed that low p53 expression correlated with higher expression of two genes associated with EMT. Increased p53 raised levels of miR-200c and the expression of a gene associated with epithelial status.

Mutations of p53 occur in more than half of cancers and loss of p53 activity correlates with poor prognosis in several cancer types. Restoring functions lost by p53 mutation by re-expressing miR-200c might be a good therapeutic strategy for treatment of p53-deficient tumors, Hung said.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. New and Delicious, Almond Butter Filled, Cookie Bites With 35.7% Protein to Help Manage Weight and Build Muscle
2. Research highlights role of protein pair in obesity regulation
3. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
4. Smithfield, United Food and Commercial Workers Union, and Food Networks Paula Deen to Deliver 150,000 Servings of Protein to San Francisco Food Bank
5. Protein Sciences Corporation Announces Profitable and Cash Flow Positive Results for 2009 and Management Realignment
6. Protein Appears Key to Intestinal Balance
7. SIBLING proteins may predict oral cancer
8. Damaged protein identified as early diagnostic biomarker for Alzheimers disease in healthy adults
9. Cells of aggressive leukemia hijack normal protein to grow
10. Omega Protein Comments on California Lawsuit Alleging Fish Oil Contaminants
11. Proteins May Predict Spread of Colon Cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Protein and microRNA block cellular transition vital to metastasis
(Date:2/5/2016)... ... ... After years as an active staff surgeon and having served as the director ... transitioned to chief of the Division of Plastic Surgery at what is now known ... began a second three-year term in January of 2016. , The original selection was ...
(Date:2/5/2016)... , ... February 05, 2016 , ... Regular gym users ... themselves having to wait longer to access the treadmills. It’s a predictable trend. After ... to lose weight and get in shape by joining gyms, starting new walking or ...
(Date:2/5/2016)... ... February 05, 2016 , ... Dr. Justin Scott and Dr. ... Annual No Cost Dental Day to individuals in need. The event is scheduled to ... No Cost Dental Day is to provide dental care to community members in need. ...
(Date:2/5/2016)... ... 05, 2016 , ... Health and wellness is a topic that should concern ... they are experiencing an illness. Migraines are a severe form of a headache and ... would not wish the pain on their worst enemy, the feeling can last for ...
(Date:2/5/2016)... ... 05, 2016 , ... –This week, Atascadero water heater company First Call ... heater. To view the report, click here or see below. , ... their pros and cons, the type chosen is almost entirely up to personal preference. ...
Breaking Medicine News(10 mins):
(Date:2/4/2016)... , Feb. 4, 2016 Frontier Pharma: ... Commercializing First-in-Class Innovation Chronic Obstructive ... with chronic inflammation of the airways and lungs. ... symptoms make the disease one of the leading ... death in the world. COPD is linked to ...
(Date:2/4/2016)... COLUMBUS, Ohio, Feb. 4, 2016 Mettler-Toledo International ... results for 2015.  Provided below are the highlights: ... the quarter compared with the prior year.  Reported sales ... in the quarter. , Net earnings per diluted ... in the prior- year period.  Adjusted EPS was $4.65, ...
(Date:2/4/2016)... 4, 2016 In response to the opioid abuse ... Commissioner for Medical Products and Tobacco, along with other FDA ... agency,s approach to opioid medications. The plan will focus on ... in pain access to effective relief. ... , Re-examine the risk-benefit paradigm for opioids and ensure that ...
Breaking Medicine Technology: