Following the tracks of AKT1 gene.
The AKT or PKB family of protein kinases is one of the best characterized targets of phosphoinositide 3-kinases or PI3Ks. The AKT/PKB signal transduction pathway regulates many growth and survival mechanisms including transcription, cell cycle progression, metabolism, apoptosis, invasion and metastasis. Recently, Carpten et al. (Nature 2007;448:439-44) reported a very interesting study on the isoform AKT1 (PKBalpha). They described a novel point mutation (E17K) in the pleckstrin homology domain (PHD) of the AKT1 gene in human breast, colorectal and ovarian cancers, and demonstrated that it induces leukemia in mice. Here we give a critical appraisal of this finding and underline its clinical impact. We also discuss possible interventions for therapeutic development of AKT inhibitors to treat human cancer.
Vogiatzi
Paraskevi
P
Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA.
Giordano
Antonio
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009857:Oncogenes; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt