Variable effects of sodium butyrate on the expression and function of the MDR1 (P-glycoprotein) gene in colon carcinoma cell lines. 1993

T O Frommel, and J S Coon, and T Tsuruo, and I B Roninson
Department of Genetics, University of Illinois at Chicago 60612-7309.

Expression of the MDR1 (P-glycoprotein) gene confers resistance to several classes of chemotherapeutic drugs (multi-drug resistance). Colon carcinomas frequently express high levels of MDR1 mRNA and P-glycoprotein, presumably reflecting the origin of these tumors from MDR1-expressing normal colonic cells. In 4 colon carcinoma cell lines (SW 620, HCT-15, DLD-1, LS 180), MDR1 expression was reported in an earlier study to be elevated after exposure to a differentiating agent, sodium butyrate (NaB). In one of these cell lines (SW 620), increased MDR1 expression reportedly was not accompanied by a decrease in the accumulation or cytotoxicity of vinblastine, a P-glycoprotein-transported drug, suggesting a possible functional abnormality of NaB-induced P-glycoprotein. We have re-examined the effect of NaB on MDR1/P-glycoprotein expression and function in the same colon carcinoma cell lines. NaB treatment induced differentiation-related changes and increased expression of MDR1 mRNA in all 4 cell lines. A major increase in MDR1 mRNA and P-glycoprotein expression was observed in only one line, SW 620. This increase, however, was accompanied by a commensurate increase in the activity of P-glycoprotein, indicating that the induced protein was fully functional. NaB treatment caused a relatively minor increase in MDR1 mRNA expressed in the other 3 cell lines. Two of these lines showed a detectable increase in the P-glycoprotein expression and function, but in the third line (LS 180) P-glycoprotein was undetectable either before or after exposure to NaB. The magnitude of MDR1 induction by NaB showed no apparent correlation with differentiation-related changes induced by this agent.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D002087 Butyrates Derivatives of BUTYRIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxypropane structure. Butyrate,n-Butyrate,Butanoic Acids,Butyric Acids,Acids, Butanoic,Acids, Butyric,n Butyrate
D002277 Carcinoma A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer." Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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