Abstract
Background3-phosphoinositide-dependent protein kinase-1 (PDK1) functions downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC family of protein kinases that are known to play crucial roles in physiological processes associated with cell metabolism, growth, proliferation and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human disease, including cancer.MethodsWe used immunohistochemical analysis to determine PDK1 expression in 241 tumors from patients with breast cancer in which we had previously analyzed PIK3CA mutation status.ResultsModerate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression.ConclusionOur findings indicate that PDK1 is independently activated in breast cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a specific and distinct role from the canonical PIK3/Akt pathway and promotes oncogenesis independently of AKT. Our data implicate PDK-1 and downstream components of the PDK-1 signaling pathway as promising therapeutic targets for the treatment of breast cancer.
Highlights
Moderate or high expression of 3-phosphoinositide-dependent protein kinase-1 (PDK1) was observed in 213 of the 241 cases (88%)
The protein kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) plays a key role in signaling pathways activated by several growth factors and hormones
The first evidence that PDK1 might be a viable target in cancer came in 2005 when Bayascas et al [1] generated transgenic mice that were hypomorphic for PDK1
Summary
Moderate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression. The protein kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) plays a key role in signaling pathways activated by several growth factors and hormones. AGC kinases are known to play crucial roles in the regulation of various physiological processes relevant to metabolism, growth, proliferation, and survival.
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