The phosphatidyl inositol 3-kinase signaling network: implications for human breast cancer.
The phosphatidyl inositol 3-kinase (PI3K)/Akt pathway is activated downstream of a variety of extracellular signals and activation of this signaling pathway impacts a number of cellular processes including cell growth, proliferation and survival. The alteration of components of this pathway, through either activation of oncogenes or inactivation of tumor suppressors, disrupts a signaling equilibrium and can thus lead to cellular transformation. The frequent dysregulation of the PI3K/Akt pathway in human cancer has made components of this pathway attractive for therapeutic targeting; however, a more comprehensive understanding of the signaling intricacies is necessary to develop pharmacological agents to target not only specific molecules, but also specific functions. Here, we review a series of experiments examining the contribution of molecules of this signaling network including PI3K, phosphatase and tensin homolog deleted on chromosome 10, integrin-linked kinase and Akt and address the significance to human breast cancer.
Dillon
R L
RL
Molecular Oncology Group and Departments of Biochemistry and Medicine, McGill University, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, Quebec, Canada.
White
D E
DE
Muller
W J
WJ
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D016023:Integrins / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D016023:Integrins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human