Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines

We measured the insulin-stimulated amount of Akt1, Akt2, and Akt3 enzymatic activities in four breast cancer cell lines and three prostate cancer cell lines. In the estrogen receptor-deficient breast cancer cells and the andr ogen-insensitive prostate cells, the amount of Akt3 enzymatic activity was approximately 20-60-fold higher than in the cells that were estrogen- or an drogen-responsive. In contrast, the levels of Akt1 and -2 were not increase d in these cells. The increase in Akt3 enzyme activity correlated with an i ncrease in both Akt3 mRNA and protein. In a prostate cancer cell line lacki ng the tumor suppressor PTEN (a lipid and protein phosphatase), the basal e nzymatic activity of Akt3 was constitutively elevated and represented the m ajor active Akt in these cells, Finally, reverse transcription-PCR was used to examine the Akt3 expression in 27 primary breast carcinomas. The expres sion levels of Akt3 were significantly higher in the estrogen receptor-nega tive tumors in comparison to the estrogen receptor-positive tumors. To see if the increase in Akt3 could be due to chromosomal abnormalities, the Akt3 gene was assigned to human chromosome 1q44 by fluorescence in situ hybridi zation and radiation hybrid cell panel analyses. These results indicate tha t Akt3 may contribute to the more aggressive clinical phenotype of the estr ogen receptor-negative breast cancers and androgen-insensitive prostate car cinomas.