MYC
1 Follower
Recent papers in MYC
The MYC onco-protein is a transcription factor that regulates cell proliferation, metabolism, protein synthesis, mitochondrial function and stem cell renewal. A region on chromosome 8q24 encompassing the MYC locus is amplified in prostate... more
The MYC onco-protein is a transcription factor that regulates cell proliferation, metabolism, protein synthesis, mitochondrial function and stem cell renewal. A region on chromosome 8q24 encompassing the MYC locus is amplified in prostate cancer, but this occurs mostly in advanced disease suggesting that MYC alterations occur late in prostate cancer. In contrast, MYC mRNA is elevated in most prostate cancers, even those of relatively low stage and grade (eg Gleason score 6) suggesting that MYC plays a role in initiation. However, since MYC protein levels are tightly regulated, elevated MYC mRNA does not necessarily imply elevated MYC protein. Thus, it is critical to determine whether MYC protein is elevated in human prostate cancer, and if so, at what stage of the disease this elevation occurs. Prior studies of MYC protein localization have been hampered by lack of suitable antibodies and controls. We utilized a new anti-MYC antibody coupled with genetically defined control experiments to localize MYC protein within human tissue microarrays consisting of normal, atrophy, PIN, primary adenocarcinoma, and metastatic adenocarcinoma. Nuclear overexpression of MYC protein occurred frequently in luminal cells of PIN, as well as in most primary carcinomas and metastatic disease. MYC protein did not correlate with gain of 8q24, suggesting alternative mechanisms for MYC overexpression. These results provide evidence that upregulation of nuclear MYC protein expression is a highly prevalent and early change in prostate cancer and suggest that increased nuclear MYC may be a critical oncogenic event driving human prostate cancer initiation and progression.
- by Bora Gurel and +1
- •
- Pathology, Cancer, Immunohistochemistry, Prostate Cancer
We have recently recapitulated metastasis of human PTEN/ TP53-mutant PC in mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by Myc-, and not Akt-activation. Here, we show that cell-cell communication... more
We have recently recapitulated metastasis of human PTEN/ TP53-mutant PC in mouse using the RapidCaP system. Surprisingly, we found that this metastasis is driven by Myc-, and not Akt-activation. Here, we show that cell-cell communication by Il6 drives the Akt-Myc switch through activation of the Akt-suppressing phosphatase Phlpp2, when Pten and p53 are lost together, but not separately. Il6 then communicates a downstream program of Stat3-mediated Myc-activation, which drives cell proliferation. Similarly in tissues, peak proliferation in Pten/ Trp53 mutant primary and metastatic PC does not correlate with activated Akt, but with Stat3/ Myc activation instead. Mechanistically, Myc strongly activates the Akt phosphatase Phlpp2 in primary cells and PC metastasis. We show genetically that Phlpp2 is essential for dictating proliferation of Myc-mediated Akt-suppression. Collectively, our data reveal competition between two proto-oncogenes: Myc and Akt, which ensnarls the Phlpp2 gene to facilitate Myc-driven PC metastasis after loss of Pten and Trp53.
- by Dawid G Nowak and +3
- •
- Molecular Biology, Genomics, Cell Biology, Cancer Biology
Because of the lack of the intrinsic regenerative capacity, the injured central nervous system (CNS) in humans does not restore the severed neural connections. Therefore, the respective body functions in affected patients never fully... more
Because of the lack of the intrinsic regenerative capacity, the injured central nervous system (CNS) in humans does not restore the severed neural connections. Therefore, the respective body functions in affected patients never fully recover. There are animals, however, who are able to readily regenerate even severe damage to major parts of their CNS. Echinoderms, a phylum of marine invertebrates, have emerged as very promising model organisms in regenerative biology, as their phylogenetic position among basal deuterostomes makes them particularly valuable for understanding the evolution of neural regeneration and also as an important source of insights into how to improve regeneration in human patients. As the first step in characterizing the gamut of molecular processes underlying efficient neural regeneration in echinoderms, we carried out a high-throughput analysis of transcriptomic changes in the regenerating radial nerve cord in the sea cucumber Holothuria glaberrima. Functional analysis of differentially expressed genes suggested a key role of the extracellular matrix remodeling and identified suppression of the glutamate excitotoxicity pathway as one of the possible adaptations contributing to the efficiency of neural regeneration. Analysis of expression of pluripotency factors showed that, surprisingly, most of them remained expressed at the constant level both in normal and regenerating tissue. Only Myc, the echinoderm homolog of the mammalian c-Myc, was highly up-regulated during regeneration. Functional analysis suggests that during the early regeneration phase, this transcription factor is required for proper dedifferentiation of glial cells and for initiation of the programmed cell death in the vicinity of the injury.
Related Topics