Figure 1.

In the cytoplasm, PTEN mediates dephosphorylation of PIP3 to PIP 2 which inhibits the PI3k/Akt/mTOR signaling pathway leading to slower tumor growth. Histone deacetylase inhibitors activate PTEN nuclear translocation, whereas DNMTs cause hypermethylation of PTEN promoter and loss of its activity, which has been described during tumor progression. Binding of p53 to the PTEN promoter induces its transcription. Additionally, BMI1 binds to the PTEN protein in the nucleus inhibiting its expression. Consequently, BMI1 reduces PTEN's ability to inhibit Akt activation in the cytoplasm. Common features observed in BLBC include mutations of the tumor suppressor Rb and the oncogene K-ras, and increased activity of Myc and HIF1α)/ARNT, leading to increased cell proliferation.