Hyperoxia inhibits proliferation of Mv1Lu epithelial cells independent of TGF-beta signaling.
High concentrations of O(2) inhibit epithelial cell proliferation that resumes on recovery in room air. To determine whether growth arrest is mediated by transforming growth factor-beta (TGF-beta), changes in cell proliferation during exposure to hyperoxia were assessed in the mink lung epithelial cell line Mv1Lu and the clonal variant R1B, which is deficient for the type I TGF-beta receptor. Mv1Lu cells treated with TGF-beta accumulated in the G(1) phase of the cell cycle as determined by propidium iodide staining, whereas proliferation of R1B cells was unaffected by TGF-beta. In contrast, hyperoxia inhibited proliferation of both cell lines within 24 h of exposure through an accumulation in the S phase. Mv1Lu cells treated with TGF-beta and exposed to hyperoxia accumulated in the G(1) phase, suggesting that TGF-beta can inhibit the S phase accumulation observed with hyperoxia alone. Cyclin A was detected in cultures exposed to room air or growth arrested by hyperoxia while decreasing in cells growth arrested in the G(1) phase by TGF-beta. Finally, hyperoxia failed to activate a TGF-beta-dependent transcriptional reporter in both Mv1Lu and R1B cells. These findings reveal that simple growth arrest by hyperoxia involves a defect in S phase progression that is independent of TGF-beta signaling.
Rancourt
R C
RC
Department of Environmental Medicine, University of Rochester, Rochester, New York 14642, USA.
Staversky
R J
RJ
Keng
P C
PC
O'Reilly
M A
MA
D000230:Adenocarcinoma; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000166:cytology*; D008175:Lung Neoplasms; D008907:Mink; D010100:Oxygen / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta; D008156:Luciferases; D010100:Oxygen