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:
*Name:
*Comment:
*Email:


(Date:6/16/2016)... 2016 The global ... reach USD 1.83 billion by 2024, according to ... Technological proliferation and increasing demand in commercial buildings, ... drive the market growth.      (Logo: ... development of advanced multimodal techniques for biometric authentication ...
(Date:6/9/2016)... TURKU, Finland , June 9, 2016 ... French National Police deploy Teleste,s video security solution to ensure ... France during the major tournament ... and data communications systems and services, announced today that its ... Police Prefecture to back up public safety across ...
(Date:6/2/2016)... LONDON , June 2, 2016 ... has awarded the 44 million US Dollar project, ... Security Embossed Vehicle Plates including Personalization, Enrolment, and IT Infrastructure ... world leader in the production and implementation of Identity Management ... in January, however Decatur was selected ...
Breaking Biology News(10 mins):
(Date:12/2/2016)... 2016 More than $4.3 million was raised last ... DHMD ). The gala was held at the American Museum ... and honored Alan Alda and ... and medicine and the public understanding of science. Since the ... event has raised $40 million for the Laboratory,s research and ...
(Date:12/2/2016)... THOUSAND OAKS, Calif. , Dec. 2, 2016 ... AGN ) today announced the submission of a ... for ABP 215, a biosimilar candidate to Avastin ® ... biosimilar application submitted to the EMA. "The ... milestone as Amgen seeks to expand our oncology portfolio," said ...
(Date:12/2/2016)... Research and Markets has announced the addition of ... to their offering. ... , , An ... is anticipated. Nanotechnology will be applied at all stages of ... applications in clinical trials. Many of the assays based on ...
(Date:12/2/2016)... Texas (PRWEB) , ... December ... ... that it will share findings demonstrating the value of DNA microarray comparative ... at this year’s San Antonio Breast Cancer Symposium. Using molecular test results ...
Breaking Biology Technology: