Navigation Links
Molecular differences between early and advanced melanomas could provide new drug targets

The cell-signaling molecule Akt is a primary trigger that leads malignant melanomas on the skin's surface to begin growing vertically beneath the skin and turn into deadly invasive cancers, scientists have found. Understanding this key molecular difference between radial melanomas that spread on the surface of the skin and melanomas that grow vertically and invasively could provide new targets for the development of drugs to treat individuals with advanced stage melanomas.

Radial melanomas that have not spread below the skin can be treated surgically and have a survival rate of 98 percent beyond five years, according to the American Cancer Society. But when melanomas grow downward, the tumors become highly resistant to chemotherapy and radiation and the five-year survival rate falls rapidly, to 64 percent if the disease has reached the lymph nodes and 16 percent if it has spread to other organs.

The discovery of Akt's significant role in the progression of melanomas was made by scientists in the Department of Dermatology at Emory University School of Medicine and published in the March issue of the Journal of Clinical Investigation. Senior author is Jack L. Arbiser, MD, PhD, and lead author is Baskaran Govindarajan, PhD.

When the scientists introduced the gene for Akt into radial growth melanoma cells, the cells expressed nearly eight times as much of the growth factor protein VEGF. VEGF is known to be a powerful stimulator of angiogenesis Ð the growth of microscopic blood vessels that nourish cancerous tumors and lead to unregulated cell growth. When melanoma cells overexpressing Akt were introduced into immunocompromised (nude) mice, the mice developed aggressive tumors that expressed high levels of VEGF, whereas a control group of mice developed no tumors.

Another result of Akt overexpression was the increased production of reactive oxygen (ROS). Reactive oxygen is created during cellular metabolism and has long been as sociated with triggering angiogenesis and the resulting growth of tumors. The scientists also found that the Akt-induced melanoma cells produced more of the enzyme NOX4, one of the NOX family of genes known to increase generation of ROS and to trigger angiogenesis.

The scientists also found that in cells with greater Akt expression, there was an increase in impaired mitochondria-- the energy factories of cells. Their research showed, however, that these mutations in mitochondria were likely the result of the prolonged exposure to increased oxidative stress caused by Akt overexpression, but that the mitochondrial mutations were not essential for the aggressive growth of melanomas induced by Akt.

"Our research shows that Akt overexpression on its own is sufficient to transform radial growth melanoma cells into highly invasive tumors via reactive oxygen pathways," says Dr. Arbiser. "This could provide us with promising targets for anti-cancer drug therapy. We will continue to work on refining the exact mechanisms of how Akt influences the aggressive growth of melanomas."

Source:Emory University

Related biology news :

1. Molecular biology fills gaps in knowledge of bat evolution
2. Molecular machine may lead to new drugs to combat human diseases
3. Molecular Motors Cooperate In Moving Cellular Cargo, Study Shows
4. Molecular models advance the fight against malaria
5. Molecular fossils uncover link between viruses and the immune system
6. Molecular thermometers on skin cells detect heat and camphor
7. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
8. Molecular steps involved in the creation of gene-silencing microRNAs identified
9. Molecular miners find pain relief drugs from the sea
10. Molecular mechanism of feather formation found
11. Molecular trigger for Huntingtons disease found

Post Your Comments:

(Date:11/18/2015)... 18, 2015 --> ... new market report titled  Gesture Recognition Market - Global ... - 2021. According to the report, the global gesture recognition market was ... to reach US$29.1 bn by 2021, at a CAGR ... North America dominated the global gesture recognition ...
(Date:11/16/2015)... Calif. , Nov 16, 2015  Synaptics ... of human interface solutions, today announced expansion of ... TouchView ™ touch controller and display driver ... revolution of smartphones. These new TDDI products add ... TD4100 (HD resolution), TD4302 (WQHD resolution), and TD4322 ...
(Date:11/10/2015)... 10, 2015  In this report, the ... of product, type, application, disease indication, and ... report are consumables, services, software. The type ... biomarkers, efficacy biomarkers, and validation biomarkers. The ... diagnostics development, drug discovery and development, personalized ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... and NEW YORK , November 24, ... investment by Bristol-Myers Squibb in a European ... Bristol-Myers Squibb Company in which the companies will work ... immuno-oncology and other areas of unmet medical need. The collaboration ... LSP 5, the latest LSP fund. This is the first ...
(Date:11/24/2015)... , Nov. 24, 2015 According to two new ... 2005. This is something that many doctors, scientists, and public ... questions remains: with fewer PSA tests being done, will there ... Dr. David Samadi, "Despite the efforts made ... remains the second leading cancer cause of death in men, ...
(Date:11/23/2015)... Nov. 23, 2015   Ceres, Inc . (Nasdaq: ... financial results for the fiscal year ended August 31, ... --> --> During fiscal ... and feed products with a better balance of yield, ... distribution agreements with several leading crop input providers and ...
(Date:11/23/2015)... Md. (PRWEB) , ... November 23, 2015 , ... ... 100 award for the development of its Nexera UC Unified Chromatography system. The ... 100 most technically significant new products of the year in the analytical and ...
Breaking Biology Technology: