14-3-3 σ expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis.
BACKGROUND
In vitro cell culture experiments with primary cells have reported that cell proliferation is retarded in the presence of ambient compared to physiological O₂ levels. Cancer is primarily a disease of aberrant cell proliferation, therefore, studying cancer cells grown under ambient O₂ may be undesirable. To understand better the impact of O₂ on the propagation of cancer cells in vitro, we compared the growth potential of a panel of ovarian cancer cell lines under ambient (21%) or physiological (3%) O₂.


RESULTS
Our observations demonstrate that similar to primary cells, many cancer cells maintain an inherent sensitivity to O₂, but some display insensitivity to changes in O₂ concentration. Further analysis revealed an association between defective G2/M cell cycle transition regulation and O₂ insensitivity resultant from overexpression of 14-3-3 σ. Targeting 14-3-3 σ overexpression with RNAi restored O₂ sensitivity in these cell lines. Additionally, we found that metastatic ovarian tumors frequently overexpress 14-3-3 σ, which in conjunction with phosphorylated RB, results in poor prognosis.


CONCLUSIONS
Cancer cells show differential proliferative sensitivity to changes in O₂ concentration. Although a direct link between O₂ insensitivity and metastasis was not determined, this investigation showed that an O₂ insensitive phenotype in cancer cells to correlate with metastatic tumor progression.
Greehey Children's Cancer Research Institute, University of Texas Health Science Center, San Antonio, Texas, United States of America.
Dashnamoorthy
D
Ravi
Yidong
Y
Chen
Bijal
B
Karia
Adam
A
Brown
Ting Ting
TT
Gu
Jie
J
Li
Mark S
MS
Carey
Bryan T
BT
Hennessy
Alexander J R
AJ
Bishop
D048948:14-3-3 Proteins / Q000235:genetics*; D002455:Cell Division; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005260:Female; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D048948:14-3-3 Proteins; D010100:Oxygen
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