S100P is selectively upregulated in tumor cell lines challenged with DNA cross-linking agents.
Bifunctional alkylating agents that cross-link DNA are implicated in the pathogenesis of therapy related myelodysplastic syndromes (MDS) and MDS related acute myeloid leukemia (MDR-AML). We exposed HL60 cells to the highest level of bifunctional alkylating nitrogen mustard mechlorethamine (HN2) that was consistent with recovery following suppressed growth. Microarray analyses showed minor changes in transcripts in HN2 treated cells. A moderate up-regulation of S100P mRNA was consistently observed after 1 day of exposure to bifunctional alkylating agents and expression was not induced with monofunctional agents. Elevated S100P protein/antigen was not detected until days later in a subset of non-mitotic G2 cells. Elevated S100P protein persisted over the course of a delayed recovery phase. The results confirm recent reports indicating that S100P is a survival factor. In addition, our results indicate that S100P has a specific role in G2 cell function associated with a prolonged phase of recovery after exposure to bifunctional alkylating agents.
Jiang
Fen
F
Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232-5310, USA.
Shults
Keith
K
Flye
Leanne
L
Hashimoto
Yuko
Y
Van Der Meer
Riet
R
Xie
Jingping
J
Kravtsov
Vladimir
V
Price
James
J
Head
David R
DR
Briggs
Robert C
RC
D000477:Alkylating Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects*; D020869:Gene Expression Profiling; D018922:HL-60 Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D007621:Karyotyping; D008466:Mechlorethamine / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D013347:Subcellular Fractions; D015854:Up-Regulation
D000477:Alkylating Agents; D002135:Calcium-Binding Proteins; D003432:Cross-Linking Reagents; D009363:Neoplasm Proteins; C103003:S100P protein, human; D008466:Mechlorethamine