RESUMO
Akt signaling may promote breast cancer progression and poor disease outcome. We hypothesized that serum insulin-like growth factor I (IGF-I) and a proinflammatory tumor environment induce phosphorylation of Akt and downstream targets of Akt in breast cancer. We studied the relationship between Akt pathway activation, IGF-I and markers of inflammation, e.g., nitric oxide synthase-2 (NOS2), cyclooxygenase-2 (COX2) and tumor phagocyte density, in 248 breast tumors. We also examined the association of Akt phosphorylation with breast cancer survival. We observed that phosphorylation of Akt, BAD and caspase-9 correlated strongly with the expression of the 2 proinflammatory enzymes, NOS2 and COX2, in breast tumors (p < 0.001; Spearman rank correlation). Both NOS2 and COX2 expression were independently associated with Akt phosphorylation in the multivariate analysis. Serum IGF-I concentrations and the IGF-I/IGFBP3 ratio correlated with Akt phosphorylation at Thr308 and Ser473 in breast tumors (p Assuntos
Neoplasias da Mama/metabolismo
, Ciclo-Oxigenase 2/metabolismo
, Inflamação/metabolismo
, Fator de Crescimento Insulin-Like I/farmacologia
, Proteínas Proto-Oncogênicas c-akt/metabolismo
, Transdução de Sinais/efeitos dos fármacos
, Animais
, Western Blotting
, Neoplasias da Mama/tratamento farmacológico
, Caspase 9/metabolismo
, Técnicas de Cocultura
, Feminino
, Humanos
, Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo
, Macrófagos/fisiologia
, Camundongos
, Pessoa de Meia-Idade
, Terapia Neoadjuvante
, Óxido Nítrico Sintase Tipo II/metabolismo
, Fagocitose
, Fosforilação/efeitos dos fármacos
, Taxa de Sobrevida
, Proteína de Morte Celular Associada a bcl/metabolismo