Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The E2A-HLF fusion gene transforms human pro-B lymphocytes by interfering with an early step in apoptotic signaling. In a search for E2A-HLF-responsive genes, we identified a zinc finger transcription factor, SLUG, whose product belongs to the Snail family of developmental regulatory proteins. Importantly, SLUG bears close homology to the CES-1 protein of C. elegans, which acts downstream of CES-2 in a neuron-specific cell death pathway. Consistent with the postulated role of CES-1 as an antiapoptotic transcription factor, SLUG was nearly as active as Bcl-2 or Bcl-xL in promoting the survival of IL-3-dependent murine pro-B cells deprived of the cytokine. We conclude that SLUG is an evolutionarily conserved transcriptional repressor whose activation by E2A-HLF promotes the aberrant survival and eventual malignant transformation of mammalian pro-B cells otherwise slated for apoptotic death.
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PMID:SLUG, a ces-1-related zinc finger transcription factor gene with antiapoptotic activity, is a downstream target of the E2A-HLF oncoprotein. 1051 15

In this study, cationic nanoparticles self-assembled from the amphiphilic copolymer poly(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate) (P(MDS-co-CES) were synthesized and used to deliver Bcl-2 targeted siRNA into HepG2, HeLa and MDA-MB-231 cell lines, and downregulate Bcl-2 mRNA expression levels. Confocal microscopic studies show that the nanoparticles were able to complex with siRNA and deliver it inside the cells efficiently, but siRNA was easily dissociated from the complexes in the cytoplasm for its biological functions. Bcl-2 mRNA expression levels as low as 10% were achieved after treatment with nanoparticle/siRNA complexes. The downregulation efficiency of Bcl-2 mRNA level was similar to that mediated by Lipofectamine but higher than that induced by PEI. PEG was also conjugated to siRNA via a cleavable disulfide bond, and nanoparticle/siRNA-PEG complexes showed no significant protein adsorption as compared with 26 and 17% for blank nanoparticles and nanoparticle/siRNA complexes, respectively. The presence of serum caused slight aggregation of nanoparticle/siRNA or nanoparticle/siRNA-PEG complexes. However, the size of the complexes was still below 250 nm after being incubated in PBS containing 10% serum for 4 h. On the other hand, PEGylated siRNA delivered by the nanoparticles downregulated Bcl-2 mRNA expression level in the cells as efficiently as unmodified siRNA. Bcl-2 protein was also downregulated efficiently by nanoparticle/siRNA complexes in all cell lines tested. The downregulation of Bcl-2 mRNA or Bcl-2 protein did not show significant cell death in the tested siRNA and polymer concentration range. However, the delivery of siRNA sensitized HeLa cells to paclitaxel treatment, yielding significant improvement over the untreated cells (p<0.05). These cationic nanoparticles may be potentially employed to downregulate Bcl-2 expression and sensitize cancer cells to anticancer drugs for more efficient chemotherapy.
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PMID:Efficient delivery of Bcl-2-targeted siRNA using cationic polymer nanoparticles: downregulating mRNA expression level and sensitizing cancer cells to anticancer drug. 1907 31

Forkhead box M1 (FOXM1) was initially identified as an oncogenic transcription factor, and multiple lines of evidence have demonstrated that FOXM1 is abundantly expressed and plays an irreplaceable role in several types of human cancers. Also, evidence has shown the association of FOXM1 with gastric carcinoma metastasis and patients prognosis; however, the potential role and molecular mechanism of FOXM1 in gastric cancer cell apoptosis are still obscure. The current study indicates that FOXM1 is highly expressed in a variety of gastric carcinoma cell lines, such as BGC823, MGC803, AGS, and SGC-7901, compared with the normal gastric mucosal epithelial cell lines CES-1. FOXM1 silence markedly inhibits AGS and SGC-7901 cell survival and proliferation, increases their apoptosis, and modulates apoptosis-related protein expression, including reduced Bcl-2 level and increased Bax and caspase-3 levels. Further study showed that FOXM1 depletion induced cell autophagy through increasing the level of beclin-1 and decreasing the P62 expression. We next corroborated that FOXM1 silence abolished the expression of Sirtuin 7 (SIRT7) and increased the level of insulin-like growth factor 2 (IGF2) and mammalian target of rapamycin (mTOR). Finally, our data documented that the SIRT7/mTOR/IGF2 pathway was involved in the function of FOXM1 in AGS cell growth and apoptosis. In conclusion, these results confirmed that FOXM1 is involved in gastric carcinoma progression via the SIRT7/mTOR/IGF2 pathway.
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PMID:Silencing forkhead box M1 promotes apoptosis and autophagy through SIRT7/mTOR/IGF2 pathway in gastric cancer cells. 2995 72