Depletion of cellular energy activates the AMP-activated kinase (AMPK) to favor energy-producing catabolic processes during tumorigenesis. Using a panel of in vitro cell lines and resected tumors, we investigated the therapeutic value of manipulating AMPK in prostate cancer (PC). Phospho-AMPK expression was significantly elevated in human PC cells and clinical PC samples. In clinical PC, we observed a trend for increasing phospho-AMPK with increasing Gleason sum score; Phospho-AMPK expression was associated with phospho-ACC (p=0.0023). Using the paired PC3 and PC3M cells to model progressive androgen-independent PC, treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR) or A-769662 suppressed proliferation, migration and invasion in both cell lines, and down-regulated mTOR and P70S6Ki levels regardless of the Akt status. Involvement of AMPK was confirmed by Compound C (AMPK inhibitor) and siRNA-mediated AMPK silencing. Despite similar functional responses in PC3 and PC3M cells, AMPK activation resulted in sustained phospho-Akt activation in PC3M cells, but not in PC3 cells. This prompted the addition of the PI3K inhibitor LY-294002 to AICAR treatment of PC3M cells in a proliferation assay. Interestingly, we found no synergistic effects upon combined treatment. Collectively, these findings support AMPK as a potential therapeutic target independent of PI3K/Akt signalling.

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Seminal vesicle (SV) amyloidosis is a well-documented histological entity, but it is observed infrequently. Its incidence is on the rise, which is probably related to the increasing use of prostate biopsies to investigate patients with elevated serum prostate-specific antigen levels. Here, we report seven cases of incidental SV amyloidosis over a 3-year period and consider their relationship to the previously suggested aetiological factors. Based on our series, we conclude that incidental localized SV amyloidosis observed in diagnostic prostate biopsies does not warrant formal investigations for systemic amyloidosis.

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Pseudomonas syringae can rapidly deploy specialized functions to deal with abiotic and biotic stresses. Host niches pose specific sets of environmental challenges driven in part by immune defenses. Bacteria use a “just-in-time” strategy of gene regulation, meaning that they only produce the functions necessary for survival as needed. Extracytoplasmic function (ECF) sigma factors transduce a specific set of environmental signals and change gene expression patterns by altering RNAP promoter specificity, to adjust bacterial physiology, structure, and/or behavior to improve chances of survival. The broadly conserved ECF sigma factor, AlgU, affects virulence in both animal and plant pathogens. Pseudomonas syringae AlgU controls expression of more than 800 genes, some of which contribute to suppression of plant immunity and bacterial fitness in plants. This review discusses AlgU activation mechanisms, functions controlled by AlgU, and how these functions contribute to P. syringae survival in plants.