Modulation of the immunophenotype of ovarian cancer cells by N,N-dimethylformamide and transforming growth factor-beta 1.
Exposure of HOC-7 ovarian adenocarcinoma cells to regulators of cell differentiation caused inducer-dependent alterations of the antigenic pattern of the cells. Immunocytochemistry revealed that N,N-dimethylformamide (DMF) elevated the membrane staining for epidermal growth factor (EGF)-receptor and for desmoplakins I and II. DMF also stimulated cytoplasmic and surface labeling for CA 125 and the deposition of fibronectin into the extracellular matrix. Stimulation of fibronectin was also seen after addition of transforming growth factor (TGF)-beta 1. These responses were quantified using a fixed-cell, enzyme-linked immunosorbent assay (ELISA) and revealed that DMF dose-dependently induced expression of EGF-receptor, CA 125, fibronectin, and desmoplakins I and II. TGF-beta 1 stimulated fibronectin and desmoplakins I and II only. Production of EGF and TGF-alpha was not affected by these inducers. Immunocytochemistry, ELISA and Western blotting showed that both inducers caused down-regulation of myc oncoproteins. DMF was more effective in changing the immunophenotype of HOC-7 cells than TGF-beta 1. Desmoplakins I and II demonstrated elevated epithelial differentiation, whereas fibronectin indicated stimulation of extracellular matrix formation. Elevated EGF-receptor could not compensate for the growth inhibition induced by DMF. The expression of myc oncoproteins was inversely related to cell proliferation. CA 125, however, seems to be unrelated to cell growth.
Grunt
T W
TW
Department of Internal Medicine, University of Vienna, Austria.
Oeller
H
H
Somay
C
C
Dittrich
E
E
Fazeny
B
B
Mannhalter
C
C
Dittrich
C
C
D015153:Blotting, Western; D003598:Cytoskeletal Proteins / Q000032:analysis; D051180:Desmoplakins; D004126:Dimethylformamide / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000032:analysis; D005109:Extracellular Matrix / Q000737:chemistry; D005260:Female; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000276:immunology* / Q000473:pathology*; D011863:Radioimmunoassay; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D004126:Dimethylformamide; D066246:ErbB Receptors