Role of the phosphatidylinositol 3-kinase/Akt and mTOR/P70S6-kinase pathways in the proliferation and apoptosis in multiple myeloma

A new selective AKT pharmacological inhibitor reduces resistance to chemotherapeutic drugs, TRAIL, all-trans-retinoic acid, and ionizing radiation of human leukemia cells

“…26 At present, it is becoming evident that activation of the PI3K / Akt axis may be important for resistance to conventional (chemotherapeutic drugs) and novel (TRAIL) therapies in patients suffering from multiple myeloma. 19,50 It should be considered, however, that there are some cases of acute myeloid leukemias in which the PTEN tumor suppressor is absent or non-functional. [51][52][53] Since PTEN is a fundamental negative regulator of Akt activity, 54 it might be that in these leukemias the Akt pathway is upregulated with a consequent resistance to multiple apoptotic stimuli, as it happens in PTENnegative prostatic cancer cell lines.…”

PTEN inhibits cell proliferation and induces apoptosis by downregulating cell surface IGF-IR expression in prostate cancer cells

“…The loss of PTEN is thought to play an important role in tumor cell proliferation and metastasis, due to a lack of control of the signaling pathways that mediate cellular processes such as apoptosis and migration (Huang and Kontos, 2002;Kandel et al, 2002;Pene et al, 2002). We stably PTEN is a dual-specificity phosphatase that can dephosphorylate lipid signaling molecules and proteins involved in tyrosine kinase receptor signaling cascades (Dupont et al, 2001;Yamada and Araki, 2001;Fernandez and Eng, 2002).…”

2-Methoxyestradiol-induced apoptosis in human leukemia cells proceeds through a reactive oxygen species and Akt-dependent process

“…Akt is involved in activation/phosphorylation of numerous downstream targets implicated in the control of apoptosis, including GSK, mTOR, procaspase-9, and Bad, among others (Pene et al, 2002;Zhao et al, 2004). Activation of Akt occurs in response to diverse noxious stimuli, including UV radiation, osmotic stress, and oxidative damage (Mockridge et al, 2000;Gao et al, 2002;Mildner et al, 2002).…”