AKT1/PKB alpha kinase is frequently elevated in human cancers and its constitutive activation is required for oncogenic transformation in NIH3T3 cells

Extensive studies have demonstrated that the Akt/AKT1 pathway is essential for cell survival and inhibition of apoptosis; however, alterations of Akt/ AKT1 in human primary tumors have not been well documented. in this report, significantly increased AKT1 kinase activity was detected in primary carci nomas of prostate (16 of 30), breast (19 of 50), and ovary (11 of 28). The results were confirmed by Western blot and immunohistochemical staining ana lyses with phospho-Ser473 A-kt antibody. The majority of AKT1-activated tum ors are high grade and stage III/IV (13 of 16 prostate, 15 of 19 breast, an d 8 of 11 ovarian carcinomas). Previous studies showed that wild-type AKT1 was unable to transform NIH3T3 cells. To demonstrate the biological signifi cance of AKT1 activation in human cancer, constitutively activated AKT1 (My r-Akt) was introduced into NIH3T3 cells. Overexpression of Myr-Akt in the s tably transfected cells resulted in malignant phenotype, as determined by g rowth in soft agar and tumor formation in nude mice. These data indicate th at AKT1 kinase, which is frequently activated in human cancer, is a determi nant in oncogenesis and a potential target for cancer intervention.