Integrin alpha 5 beta 1 suppresses apoptosis triggered by serum starvation but not phorbol ester in MCF-7 breast cancer cells that overexpress protein kinase C-alpha.
MCF-7 breast cancer cells grow as adherent cells, but following overexpression of protein kinase C-alpha these cells (MCF-7-PKC-alpha cells) become anchorage-independent and exhibit increased tumorigenicity in nude mice. MCF-7-PKC-alpha cells are also sensitized to apoptosis in response to phorbol ester but not serum starvation. Flourescence-activated cell sorting revealed that several integrin subunits were down-regulated in MCF-7-PKC-alpha cells, however, the fibronectin receptor alpha 5 beta 1 was upregulated. MCF-7-PKC-alpha cells growing under non-adherent conditions underwent cell death when antibodies to alpha 5 beta 1 were added to growth media lacking serum but not when serum was present. Addition of soluble fibronectin to cells incubated without serum suppressed apoptosis triggered by anti-alpha 5 beta 1 antibodies but not by phorbol esters. MCF-7-PKC-alpha cells also were shown to express more fibronectin on their cell surface than MCF-7V cells (MCF-7 cells transfected with pSV(2)M(2)6 vector only). This study indicates that the survival of MCF-7-PKC-alpha cells under non-adherent conditions in the absence of serum results from the ligation of alpha 5 beta 1 with surface-bound fibronectin, which may account, in part, for the increased aggressiveness of these cells.
Noti
J D
JD
Laboratory of Molecular Biology, Guthrie Research Institute, Sayre, PA 18840, USA. jnoti@inet.guthrie.org
Johnson
A K
AK
D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D016895:Culture Media, Serum-Free; D004347:Drug Interactions; D005353:Fibronectins / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000096:biosynthesis / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D017469:Receptors, Fibronectin / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D016895:Culture Media, Serum-Free; D005353:Fibronectins; D007527:Isoenzymes; D010703:Phorbol Esters; D017469:Receptors, Fibronectin; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha