A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells

Caroline Craig, Robert Wersto, Min Kim, Ekta Ohri, Zhuangwu Li, Dai Katayose, Su Jae Lee, Jane Trepel, Kenneth Cowan, Prem Seth

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

In order to elucidate the biochemical mechanisms by which the universal cyclin kinase inhibitor p27(Kip1) 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.

Original languageEnglish (US)
Pages (from-to)2283-2289
Number of pages7
JournalOncogene
Volume14
Issue number19
DOIs
StatePublished - Jan 1 1997

Fingerprint

Cyclins
Cell Cycle Checkpoints
Adenoviridae
Human Activities
Breast Neoplasms
Phosphotransferases
Cyclin B1
Human Adenoviruses
Cyclin-Dependent Kinases
Poisons
Growth
Infection
S Phase
Genetic Therapy
Cell Cycle
Cell Line
DNA

Keywords

  • Cell cycle
  • Cell growth
  • Cyclin kinase inhibitors
  • G/S arrest

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. / Craig, Caroline; Wersto, Robert; Kim, Min; Ohri, Ekta; Li, Zhuangwu; Katayose, Dai; Lee, Su Jae; Trepel, Jane; Cowan, Kenneth; Seth, Prem.

In: Oncogene, Vol. 14, No. 19, 01.01.1997, p. 2283-2289.

Research output: Contribution to journalArticle

Craig, C, Wersto, R, Kim, M, Ohri, E, Li, Z, Katayose, D, Lee, SJ, Trepel, J, Cowan, K & Seth, P 1997, 'A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells', Oncogene, vol. 14, no. 19, pp. 2283-2289. https://doi.org/10.1038/sj.onc.1201064
Craig, Caroline ; Wersto, Robert ; Kim, Min ; Ohri, Ekta ; Li, Zhuangwu ; Katayose, Dai ; Lee, Su Jae ; Trepel, Jane ; Cowan, Kenneth ; Seth, Prem. / A recombinant adenovirus expressing p27(Kip1) induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. In: Oncogene. 1997 ; Vol. 14, No. 19. pp. 2283-2289.
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