title: A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells.
abstract: In order to elucidate the biochemical mechanisms by which the universal cyclin kinase inhibitor p27Kip1 regulates cell cycle progression in human breast cancer cells, a recombinant adenovirus expressing human p27 was constructed (Adp27). Upon infection of human breast cancer cells MDA-MB-231 and MCF-7 with Adp27, a high level of p27 expression was observed, and this resulted in a marked decrease in the proportion of cells in S-phase. In multiple cell lines, comparison of the cytotoxicity of Adp27 with another adenovirus vector expressing the related universal cyclin kinase inhibitor WAF1/Cip1 (AdWAF1), showed Adp27 to be markedly more (up to 56-fold) toxic than AdWAF1. DNA histograms showed Adp27 to cause a G1/S arrest at lower viral doses than AdWAF1. Analysis of cyclin dependent kinase activity following Adp27 infections showed decreased Cdk2 and cyclin B1-Cdc2 activity at lower viral doses when compared with AdWAF1. Adp27 is therefore potentially useful for studies of growth regulation and for gene therapy when growth inhibition is desired.
authors.affiliation: Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: C
authors.initials: C
authors.lastname: Craig
authors.forename: R
authors.initials: R
authors.lastname: Wersto
authors.forename: M
authors.initials: M
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: Ohri
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: D
authors.initials: D
authors.lastname: Katayose
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Trepel
authors.forename: K
authors.initials: K
authors.lastname: Cowan
authors.forename: P
authors.initials: P
authors.lastname: Seth
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases