PDK then phosphorylates and activates Akt, which in turn regulates downstream signalling proteins involved in cell survival, cell growth, cell cycle progression and apoptotic response ( Vanhaesebroeck and Alessi, 2000). Then PIP3 recruits other signalling components such as Akt and PDK. PIP3 levels are tightly regulated by the phosphatase PTEN, which removes phosphate from the 3-OH position. These receptors engage the heterodimeric phosphoinositol 3-kinase (PI3K), which phosphorylates phosphatidylinositol-4, 5-bisphosphate to convert PIP2 to PIP3. Akt is a signalling component of the tyrosine kinase growth factor receptors and G-coupled receptors. Members of this family, Akt-1, Akt-2 and Akt-3, share 80% homology. In mammals, three genes have been identified encoding for the isoforms of the serine/threonine protein kinase B family, or Akt. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Kaplan–Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion.
Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion.
Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens.
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