Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology

There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation,the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally,one would merge the understandability,exactness,simplicity,and testability of the molecular biological approach,with the larger amounts of data,simultaneous consideration of multiple alterations,consideration of genes both of known interest along with the novel,cross-sample comparisons among cell lines and patient samples,and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic,attempts to do so are ongoing,and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60,the Broad Institute's Cancer Cell Line Encyclopedia,and the Wellcome Trust Sanger Institute's Cancer Genome Project,as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research,with the desired goal being improved translational understanding and application.

Transient expression of inactive RB in mesenchymal stem cells impairs their adipogenic potential and is associated with hypermethylation of the PPARγ2 promoter

The retinoblastoma gene product(pRb)is a chromatin-associated protein that can either suppress or promote activity of key regulators of tissue-specific differentiation.We found that twelve weeks after transfection of the exogenous active(ΔB/X andΔр34)or inactive(ΔS/N)forms of RB into the 10T1/2 mesenchymal stem cells and clonal selection not a single cell line did contain exogenous RB,despite being G-418 resistant.However,the consequences of the transient production of exogenous RB had different effects on the cell fate.TheΔB/X andΔр34 cells transfected with active form of RB showed elevated levels of inducible adipocyte differentiation(AD).On the contrary,theΔS/N cells transfected with inactive RB mutant were insensitive to induction of AD associated with abolishing of expression of the PPARγ2.Additionally,the PPARγ2 promoter in undifferentiatedΔS/N cells was hypermethylated,but all except−60 position CpG became mostly demethylated after cells exposure to AD.We conclude that while transient expression of inactive exogenous RB induces long term epigenetic alterations that prevent adipogenesis,production of active exogenous RBs results in an AD-promoting epigenetic state.These results indicate that pRb is involved in the establishment of hereditary epigenetic memory at least by creating a methylation pattern of PPARγ2.