Growth inhibition by anchorage-deficiency is associated with increased level but reduced phosphorylation of mutant p53.
Human breast carcinoma MCF-7 cells seeded on type I collagen-coated dishes were provided with an anchor via the collagen receptor, integrin, and grew as actively as those in plastic tissue culture dishes. In contrast, cells seeded on a layer of soft agar became anchorage-deficient and their growth was significantly inhibited, although the cell viability and the cell cycle distribution were unaffected. Immunoprecipitation analysis revealed that mutant p53 was phosphorylated at tyrosine in the anchorage-provided cells. In contrast, the p53 in the anchorage-deficient cells was present in 2-fold greater amount, but was phosphorylated to a lesser extent. Addition of a potent protein-tyrosine kinase inhibitor, herbimycin A, to the anchorage-provided cells caused an elevated level of p53, and inhibitions of cell proliferation and p53 phosphorylation, without interfering with the cell adhesion to the substratum. These results demonstrated that the growth inhibition by anchorage-deficiency or by herbimycin A is associated with an elevated p53 level and reduced p53 phosphorylation at tyrosine.
Takahashi
K
K
Department of Biochemistry, Kanagawa Cancer Center Research Institute, Yokohama.
Suzuki
K
K
Uehara
Y
Y
Ono
T
T
D000596:Amino Acids / Q000032:analysis; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D001345:Autoradiography; D016227:Benzoquinones; D001943:Breast Neoplasms; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D016158:Genes, p53; D006801:Humans; D047029:Lactams, Macrocyclic; D009154:Mutation; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D011809:Quinones; D016159:Tumor Suppressor Protein p53; D017828:Rifabutin; C020754:herbimycin