Integration of the analyses uncovered that frequently mutated or amplified/deleted genes were involved in the KRAS/phosphatidylinositol 3-kinase (82%) and MYC/retinoblastoma (75%) pathways as well as the critical chromatin remodeling complex switch/sucrose nonfermentable (85%).
Overexpression of human MYCN in the context of Rb inactivation increased the expression of MYC-, E2F-, and ribosome-related gene sets, promoted excessive proliferation, and led to retinoblastoma with anaplastic changes.
Furthermore, we showed that CA promoted proteasomal degradation of several substrate proteins, including Cyclin B1, retinoblastoma (RB), SOX2, and glial fibrillary acid protein (GFAP), whereas MYC levels were not modified.
We determined whether mt-Rb activated the Myc promoter in the HTP9 cells and demonstrated that mt-Rb acted as an inhibitor of wild-type Rb-induced repression on the Myc promoter.
This RbAp48-mediated transformation of HPV16 is probably because of the regulation by RbAp48 of tumor suppressors retinoblastoma and p53, apoptosis-related enzymes caspase-3 and caspase-8, and oncogenic genes, including E6, E7, cyclin D1 (CCND1), and c-MYC.
We studied the expression of selected tumor suppressor genes (P53 and retinoblastoma [RB]), oncogenes (MYC and BCL2), and a transferrin-receptor related protein (Trump) in sequential biopsies in 16 patients.
In addition, we studied the c-myc gene for rearrangements by Southern blotting and assessed expression of the retinoblastoma (Rb) and p53 genes by immunostaining.
These findings raise questions about the functional role of the RB:MYC interactions and emphasize important differences in the binding patterns between MYC and the other RB-associated proteins.