Molecular imaging of Akt kinase activity.
The serine/threonine kinase Akt mediates mitogenic and anti-apoptotic responses that result from activation of multiple signaling cascades. It is considered a key determinant of tumor aggressiveness and is a major target for anticancer drug development. Here, we describe a new reporter molecule whose bioluminescence activity within live cells and in mice can be used to measure Akt activity. Akt activity in cultured cells and tumor xenografts was monitored quantitatively and dynamically in response to activation or inhibition of receptor tyrosine kinase, inhibition of phosphoinositide 3-kinase, or direct inhibition of Akt. The results provide unique insights into the pharmacokinetics and pharmacodynamics of agents that modulate Akt activity, revealing the usefulness of this reporter for rapid dose and schedule optimization in the drug development process.
Zhang
Limin
L
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Lee
Kuei C
KC
Bhojani
Mahaveer S
MS
Khan
Amjad P
AP
Shilman
Alla
A
Holland
Eric C
EC
Ross
Brian D
BD
Rehemtulla
Alnawaz
A
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D017931:DNA Primers; D005784:Gene Amplification; D017930:Genes, Reporter; D005910:Glioma; D006258:Head and Neck Neoplasms; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D010957:Plasmids; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D017931:DNA Primers; D011994:Recombinant Proteins; D051057:Proto-Oncogene Proteins c-akt