title: IGFBP-3 prolongs the p53 response and enhances apoptosis following UV irradiation.
abstract: Neoplastic transformation is characterised by an imbalance in favour of cell growth over programmed cell death (apoptosis). The tumour-suppressor gene p53, responsible for maintaining cell-cycle control, is mutated in the majority of human cancers. Loss of function of the target genes of p53 are therefore important in tumourigenesis. One such target gene is the insulin-like growth factor binding protein-3 (IGFBP-3), an extracellular protein responsible for the carriage of IGF-I but which can act independently of IGF-I, inhibiting cell growth and enhancing apoptosis. Using the KYSE 190 oesophageal carcinoma cell line, we have demonstrated that IGFBP-3 alone has no effect on cell growth or cell survival. However, it significantly enhanced apoptosis, with a 67% increase in the pre-G1 peak on flow cytometry following UV irradiation. The increase in p53 was enhanced and prolonged when cells are stressed in the presence of IGFBP-3. These data suggest an autocrine/paracrine feedback loop exists between IGFBP-3 and p53, which may provide the social control necessary to maintain normal tissue homeostasis.
authors.affiliation: Division of Surgery, Bristol Royal Infirmary, United Kingdom.
authors.forename: A D
authors.initials: AD
authors.lastname: Hollowood
authors.forename: T
authors.initials: T
authors.lastname: Lai
authors.forename: C M
authors.initials: CM
authors.lastname: Perks
authors.forename: P V
authors.initials: PV
authors.lastname: Newcomb
authors.forename: D
authors.initials: D
authors.lastname: Alderson
authors.forename: J M
authors.initials: JM
authors.lastname: Holly
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology*; D013002:Somatomedins / Q000032:analysis / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D013002:Somatomedins; D016159:Tumor Suppressor Protein p53