Effects of tumor promoters on growth and on cellular redistribution of phospholipid/Ca2+-dependent protein kinase in human breast cancer cells.
Active, structurally unrelated tumor promoters (12-0-tetradecanoyl-phorbol-13-acetate (TPA), teleocidin and aplysiatoxin) inhibit growth of mammary carcinoma cells (MCF7- greater than BT-20 greater than MDA-MB-231 greater than = ZR-75-1 greater than HBL-100). This efficiency in inhibiting cell growth correlates with the tumor-promoting activity of a series of phorbol ester derivatives. The phospholipid/calcium-dependent protein kinase (PKC), a target for phorbol ester action, was measured by polyacrylamide gel electrophoresis. The levels of PKC were higher (p less than 0.001) in estrogen-receptor-negative than in estrogen-receptor-positive cells. Treatment of cells with active tumor promoters results in time- and dose-dependent translocation of cytosolic PKC to membrane fractions. Less potent phorbol esters induce only partial translocation of PKC (i.e., decrease of cytosolic without increase in membrane-bound PKC), whereas inactive esters have no effect. No correlation was found between PKC concentration or the amount of PKC translocated to membranes and the sensitivity of the respective cells to TPA. It is concluded that tumor-promoter-mediated growth inhibition of breast cancer cell lines is due to mechanism(s) occurring after the translocation of PKC.
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002273:Carcinogens / Q000494:pharmacology*; D002451:Cell Compartmentation / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008235:Lyngbya Toxins / Q000494:pharmacology; D008566:Membranes / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D008235:Lyngbya Toxins; D011960:Receptors, Estrogen; C022176:teleocidins; C006610:aplysiatoxin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate