Integrin-dependent amplification of the G2 arrest induced by ionizing radiation

Celeste L. Kremer, Monika Schmelz, Anne E Cress

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The progressive loss of laminin 5 and the α6β4 integrin is a characteristic of the transition of prostatic intraepithelial neoplasia (PIN) to invasive human prostate cancer. Our objective was to determine if the loss of the interaction with laminin 5 would influence the ability of human epithelial cells to respond to DNA damage. Three cellular damage responses to ionizing radiation (IR) were analyzed including G2 progression, cdc2 phosphorylation, and cell survival. The adhesion of normal human prostate epithelial cells to laminin 5 amplified the G2 arrest induced by IR, and depends on a known cell binding domain of laminin 5. The alteration of G2 arrest was confirmed by an inhibition of phospho-cdc2 nuclear translocation. In contrast, a prostate epithelial cancer cell line blocked in G2 independent of adhesion to laminin 5. The survival of these cell lines in response to IR was unaffected by adhesion to laminin 5. These results suggest that cell adhesion to laminin 5 in normal cells will amplify the IR induced G2 cell cycle progression block without altering cell survival. The loss of laminin 5 and the α6β4 integrin in PIN lesions may contribute to the selection and progression of genetically unstable cell types via attenuation of a DNA damage induced G2 arrest.

Original languageEnglish (US)
Pages (from-to)88-96
Number of pages9
JournalProstate
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

Ionizing Radiation
Integrins
Prostatic Intraepithelial Neoplasia
Epithelial Cells
DNA Damage
Prostatic Neoplasms
Cell Survival
Cell Line
kalinin
Cell Adhesion
Prostate
Cell Cycle
Phosphorylation

Keywords

  • α6β4 integrin
  • Cell cycle
  • Ionizing radiation
  • Laminin 5
  • Phospho-cdc2

ASJC Scopus subject areas

  • Urology

Cite this

Integrin-dependent amplification of the G2 arrest induced by ionizing radiation. / Kremer, Celeste L.; Schmelz, Monika; Cress, Anne E.

In: Prostate, Vol. 66, No. 1, 01.01.2006, p. 88-96.

Research output: Contribution to journalArticle

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