Abstract
Annexin A2 was recently identified as a paracrine factor that mediates, in part, the anchorage-independent growth (AIG) response to low dose radiation (Weber et al., Rad. Res, in press, 2009). Paracrine-dependent AIG did not fully account for the low dose radiation AIG response and we undertook a genomics approach to identify additional sensitive markers of AIG responses. Our experimental design exploited irreversible regulation of AIG by 12-O-tetradecanoyl phorbol-13-acetate (TPA), relative to reversible regulation of AIG by basic fibroblast growth factor (bFGF). 142 differentially expressed genes were common to colonies arising from bFGF- and TPA-treated JB6 cells. The majority of genes exhibited comparable patterns of regulation in terms of increased or decreased expression, while 30 genes exhibited reciprocal regulation patterns. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) expression were increased in both bFGF- and TPA-induced colonies. Ectopic expression of human DBP and HLF increased low dose X-ray radiation (10 cGy)-, TPA- and bFGF-induced AIG responses. HLF and DBP expression were increased in human basal cell carcinoma tumor tissue, relative to paired uninvolved tissue from the same donor. HLF and DBP mRNA expression were also increased in a normal human skin equivalent model system (MatTek). Collectively, our approach has identified sensitive candidate biomarkers of the AIG response that are expected to enable detailed investigations of possible risk factors for radiation carcinogenesis.
