S100P Is Selectively Upregulated In Tumor Cell Lines Challenged With DNA Cross-Linking Agents

Abstract

Bifunctional alkylating agents that cause DNA cross-linking are implicated in the pathogenesis of myelodysplastic syndrome (MDS) and MDS related acute myeloid leukemia (MDR-AML). Therefore, characterizing hematopoietic cell responses to DNA cross-link damage may be relevant to elucidating the molecular pathogenesis of MDS and MDR-AML. To search for genes selectively involved in the cellular response to DNA cross-linking agents, HL-60 cells were treated with bifunctional cross-linking agents. In cDNA microarray gene expression profiles, S100P mRNA was selectively upregulated in bifunctional alkylating agent treated HL-60 cells but not in cells treated by monofunctional agents. This upregulation was confirmed by virtual Northern blot and real time PCR analysis and was both drug dose and time dependent. S100P protein was induced with kinetics similar to that of S100P mRNA. The upregulation of S100P by HN2 suggests that it may have a role in the cellular response to cross-link DNA damage and pathogenesis of MDS and AML.