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
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13-Dec-2004