Emerging evidence suggests that oncogenes and tumor suppressors can influence tumor development not only via cell-autonomous functions in regulating proliferation/apoptosis but also via direct modulation of angiogenesis regulators.
In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed.
A recent study of microRNA signature of prion-induced neurodegeneration [64] has shown that EGR1, E2F1 and MAZ might be also implicated in the putative deregulation of immune response related genes by miRNAs via modulation of transcriptional regulators in scrapie-infected mice.
Monitoring gene expression changes during commitment again indicated that commitment was mediated by stochastic and independent modulation of key regulators.
Discordant results were also obtained when studying the modulation of apoptosis regulators upon incubation of CLL cells from CD38 high-risk patients with CD31-transfected fibroblasts [ 104, 105].
To determine the effects of rhHsp72 on the modulation of apoptosis regulators, the protein levels of Bcl-2 and Bax in the liver were measured.
After transiently silencing AGR2 or stimulating with recombinant AGR2, modulation of key regulators of growth and survival pathways was assessed with Western blot.
Mechanistically, synergy was explained by enhanced induction of caspase-dependent apoptosis, mitochondrial depolarization and modulation of key regulators of extrinsic and intrinsic cell death pathways, including c-FLIP, BIM, BAX, clusterin, Mcl-1 and several IAP family members.
Human cell lines have been engineered with stably transfected reporter genes, allowing them to assess modulation of transcription regulators such as NF-κB, AP-1, or PPAR-γ, or production of proteins such as TSLP, TGF-β, or Fiaf.
In the last decade, to trace the way for developing innovative anti-cancer therapies, several groups focused their pre-clinical research on the modulation of epigenetic regulators often aberrantly expressed in cancer.
