Gene expression profiling of six MEF cell genotypes (wild type, β2SP+/-, β2SP-/-, SMAD3+/-, SMAD3-/-, and β2SP+/-; SMAD3+/-)

Gene expression profiling was carried out in six (wild type, β2SP+/-, β2SP-/-, SMAD3+/-, SMAD3-/- and β2SP+/-/ SMAD3+/-) different mouse knockout embryonic fibroblast (MEF) cells. Beta-2-spectrin (β2SP) is a dynamic intracellular non-pleckstrin homology (PH)-domain protein that belongs to a family of polypeptides that have been implicated in conferring cell polarity. Spectrins have been linked to multiple signaling pathways, including cell cycle regulation, DNA repair and TGFβ signaling. In this study, we report a major role of the TGFβ/Smad3 adaptor β2-Spectrin in conserving genomic integrity from alcohol-induced DNA damage and describe a novel pathway that protects genomes from genotoxic stresses. To determine the mechanism for the oncogenic switch, and whether it is related to the role of β2SP in TGF-β signaling transduction or secondary to its cytoskeletal functions, we analyzed disruption of two elements of the TGF-β pathway by generating double heterozygous Sptbn1+/−/Smad3+/− mice.