Integrin-dependent amplification of the G2 arrest induced by ionizing radiation.
The progressive loss of laminin 5 and the alpha6beta4 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 alpha6beta4 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.
Kremer
Celeste L
CL
Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
Schmelz
Monika
M
Cress
Anne E
AE
D002448:Cell Adhesion; D002460:Cell Line; D004249:DNA Damage; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000502:physiology / Q000528:radiation effects; D016195:G2 Phase / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D039161:Integrin alpha6beta4 / Q000502:physiology*; D016023:Integrins / Q000502:physiology*; D008297:Male; D011467:Prostate / Q000166:cytology* / Q000502:physiology / Q000528:radiation effects*; D011839:Radiation, Ionizing
D039161:Integrin alpha6beta4; D016023:Integrins