Featured Research

from universities, journals, and other organizations

Study Suggests Akt3 Protein Is Key To Melanoma's Resistance To Chemotherapy

Date:
December 28, 2004
Source:
Penn State
Summary:
Wiping out a protein in skin cancer cells could significantly stall melanoma tumor development and increase the sensitivity of the cancer cells to chemotherapy, a Penn State College of Medicine study suggests.

HERSHEY, PA -- Wiping out a protein in skin cancer cells could significantly stall melanoma tumor development and increase the sensitivity of the cancer cells to chemotherapy, a Penn State College of Medicine study suggests.

Related Articles


The protein, Akt3, appears to be responsible for promoting tumor cell survival and development in 43 percent to 60 percent of non-inherited melanomas.

"Our study showed that lowering Akt3 activity can reduce the tumor-creating potential of melanoma cells by making the cancer cells more likely to respond to signals that tell them to die," said Gavin P. Robertson, Ph.D., assistant professor of pharmacology, pathology and dermatology, Penn State College of Medicine. "Because most chemotherapeutic drugs work by inducing apoptosis, or programmed cell death, we predict that inhibiting Akt3 activity could lower the threshold doses of drugs or radiation required for effective chemo- or radiotherapy and provide a mechanism to directly target the melanoma cells."

The study, published recently in the journal Cancer Research, used melanoma cell lines together with tumors taken directly from melanoma patients to show that as melanoma cells become more aggressive and metastatic, the amount of active Akt3 protein in the cells increases.

In non-cancerous cells, another protein called PTEN – phosphatase and tensin homologue – starts a chain reaction ensuring that malfunctioning and damaged cells are killed. But abnormal cancerous cells gain the ability to switch off PTEN, allowing dysfunctional, cancerous cells to survive and thrive.

This study exposes another link in that chain reaction by connecting PTEN to Akt3 in melanomas. Robertson found that PTEN specifically regulates Akt3. Consequently, when PTEN is lost, Akt3 malfunctions and accumulates, allowing melanoma cells to survive.

"In addition to the connection to PTEN, we also found that more copies of the Akt3 gene are present as melanoma cells become more aggressive," Robertson said. "The Akt3, in effect, protects the cancer cells from the normal signals that would tell them to die. Using samples of human melanoma tumors, we found that levels of active Akt3 increase progressively during melanoma tumor progression with highest levels present in advanced-stage melanoma."

Akt3 is one of a trio of Akt proteins, all three of which have been implicated in various cancers. For example, Akt2 activity has been found in cancers of the ovary, pancreas, stomach and breast. Although all three forms of Akt are present in melanoma cells, this study found that in melanoma, Akt1 and Akt2 remain inactive and, therefore, have little if any role in melanoma development.

Robertson used siRNA, small interfering ribonucleic acids, which can be made to reduce the amount of a specific protein produced by a cell disrupting the synthesis of the protein. In Robertson's study, the siRNA were designed specifically to target Akt3. In addition, he put back the PTEN protein in the melanoma cells. This restarted the normal signals triggering cell death that had been halted by the melanoma cells. Both of these methods reduced melanoma cell survival and inhibited tumor development. Robertson's team confirmed this using a mouse model, finding that decreasing Akt3 activity using siRNA or reintroducing the missing PTEN protein halted tumor progression.

"Identifying Akt3 as a possible target to halt the growth of and kill melanoma cells provides new opportunities to develop therapies for patients with metastatic melanoma," Robertson said. "Ultimately, therapies targeted against Akt3 could be used with traditional chemotherapy to give those with melanoma more effective therapeutic options to fight the disease."

This research was supported by the American Cancer Society and The Foreman Foundation for Melanoma Research.

In addition to Robertson, the study team included: Jill M. Stahl, Arati Sharma, Mitchell Cheung, Melissa Zimmerman, Mark Kester, and Lakshman Sandirasegarane, Penn State College of Medicine, Jin Q. Cheng, University of South Florida College of Medicine, and Marcus W. Bosenberg, The University of Vermont.


Story Source:

The above story is based on materials provided by Penn State. Note: Materials may be edited for content and length.


Cite This Page:

Penn State. "Study Suggests Akt3 Protein Is Key To Melanoma's Resistance To Chemotherapy." ScienceDaily. ScienceDaily, 28 December 2004. <www.sciencedaily.com/releases/2004/12/041220013019.htm>.
Penn State. (2004, December 28). Study Suggests Akt3 Protein Is Key To Melanoma's Resistance To Chemotherapy. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2004/12/041220013019.htm
Penn State. "Study Suggests Akt3 Protein Is Key To Melanoma's Resistance To Chemotherapy." ScienceDaily. www.sciencedaily.com/releases/2004/12/041220013019.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins