title: The RNA/DNA-binding protein PSF relocates to cell membrane and contributes cells' sensitivity to antitumor drug, doxorubicin.
abstract: Cell surface proteins play an important role in multidrug resistance (MDR). However, the identification involving chemoresistant features for cell surface proteins is a challenge. To identify potential cell membrane markers in hematologic cancer MDR, we used a cell- and antibody-based strategy of subtractive immunization coupled with cell surface comparative screening of leukemia cell lines from sensitive HL60 and resistant HL60/DOX cells. Fifty one antibodies that recognized the cell surface proteins expressed differently between the two cell lines were generated. One of them, the McAb-5D12 not only recognizes its antigen but also block its function. Comparative analysis of immunofluorescence, flow cytometry, and mass spectrum analysis validated that the membrane antigen of McAb-5D12 is a nucleoprotein-polypyrimidine tract binding protein associated splicing factor, PSF. Our results identified that PSF overexpressed on the membrane of sensitive cells compared with resistant cells and its relocation from the nuclear to the cell surface was common in hematological malignancy cell lines and marrow of leukemia patients. Furthermore, we found that cell surface PSF contributed to cell sensitivity by inhibiting cell proliferation. The results represent a novel and potentially useful biomarker for MDR prediction. The strategy enables the correlation of expression levels and functions of cell surface protein with some cell-drug response traits by using antibodies.
authors: Department of Hematology, National Center for Clinical Laboratories and Beijing Hospital of the Ministry of Health, Beijing, 100730, China.
authors: Simei
authors: S
authors: Ren
authors: Ming
authors: M
authors: She
authors: Min
authors: M
authors: Li
authors: Qi
authors: Q
authors: Zhou
authors: Rong
authors: R
authors: Liu
authors: Hong
authors: H
authors: Lu
authors: Chunzheng
authors: C
authors: Yang
authors: Dongsheng
authors: D
authors: Xiong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D021381:Protein Transport; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; D004317:Doxorubicin
keywords: antibody; cell drug response; cell surface target; subtractive immunization