Antiproliferative and survival properties of PMA in MCF-7 breast cancer cell.
Although PKCs are assumed to be the main targets of phorbol esters (PMA), additional PMA effectors, such as chimaerins (a family of RacGTPase activating proteins) and RasGRP (exchange factor for Ras/Rap1), can counteract or strengthen the PKC pathways. In this study, we evaluated the proliferative behavior of PMA-treated MCF-7 breast cancer cell and found that: PMA induced growth arrest and inhibited cell death; PMA activated ERKs, which, in turn, induced p21; and inhibitors of ERK (PD98059) and PKC (GF109203X) prevented p21 induction and abolished the PMA survival effect. We conclude that PMA inhibits MCF-7 cell growth and simultaneously stimulates cell survival; both responses are linked to ERK-dependent and p53-independent p21 induction.
Fortino
V
V
Department of Physiology, University of Siena, Siena, Italy.
Torricelli
C
C
Capurro
E
E
Sacchi
G
G
Valacchi
G
G
Maioli
E
E
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D010703:Phorbol Esters / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D054462:p21-Activated Kinases / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010703:Phorbol Esters; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; D054462:p21-Activated Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one