In a previous report, we showed that increased activation of Akt, a downstream effector of phosphoinositide 3-kinase (PI3K) together with decreased activation of extracellular-signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase (MAPK) family, predicted poor clinical outcome in prostate cancer (Kreisberg et al.2004 Cancer Research 64 5232-5236).
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays important roles for prostate cancer cell survival, and the androgen receptor (AR) plays essential roles for prostate cancer cell proliferation.
We compared the involvement of PI3K/PTEN/Akt signaling in the regulation of the cell-cycle regulator p27(kip1) and investigated the mechanism of PI3K/PTEN/Akt modulation of p27(kip1) in the prostate cancer cell lines LNCaP, PC346, PC3, and DU145.
These findings suggest that the PI3K-Akt cell growth survival pathway and its downstream-regulated gene, p21(WAF/CIP), are targets for developing novel therapies against prostate cancer, especially those androgen-independent diseases.
Taken together, these results suggest that aberrant activation of PI3K-Akt pathway may contribute to increased cell invasiveness and facilitate prostate cancer progression.
Identification of genes potentially involved in the acquisition of androgen-independent and metastatic tumor growth in an autochthonous genetically engineered mouse prostate cancer model.
We explored possible interactions with body mass index and components in the IGF-1 pathway including IGFBP3, PI3k, and PTEN but none of these factors influenced the relation between IRS-1 genotype and prostate cancer risk.
The data suggest that PI3K/Akt-NF-kappaB axis may promote PC bone metastasis in part by regulating transcription and activation of the BMP-2-Smad signaling cascade in osteotropic PC cells.
These results suggest that genetic alterations in the PI3K pathway are common in prostate cancer, and occur mainly through PIK3CA amplification and PTEN hemizygous or homozygous deletion.
However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)-mediated cell growth signal transduction in PCa have yet to be elucidated in detail.
The Sex-determining region Y-box 4 and homeobox C6 transcriptional networks in prostate cancer progression: crosstalk with the Wnt, Notch, and PI3K pathways.
Increased p110beta expression in PCa may be required for RTK-independent PI3K pathway activation in adult prostate epithelium with genetic or epigenetic PTEN down-regulation.
Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls.
Recent studies suggest that targeting PTEN/PI3K/Akt and mTOR signaling pathway could be an effective strategy for the treatment of hormone refractory CaP.
Here, we show that inhibition of PI3K activity by the dual PI3K/mTOR inhibitor NVP-BEZ235 leads to a decrease in the population of CD133(+)/CD44(+) prostate cancer progenitor cells in vivo.
Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells.