Molecular basis for maize as a risk factor for oesophageal cancer in a South African population via a prostaglandin E2 positive feedback mechanism


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Ryan C. Pink1, Tracey A. Bailey1, Jehu E. Iputo2, Alastair M. Sammon3, Anthony C. Woodman1

1Cranfield Health, Cranfield University, Bedfordshire, UK, 2Dept of Physiology, Faculty of Health Sciences, Walter Sisulu University, Mthatha, South Africa, 3Dept of Surgery, Gloucestershire Royal Hospital, Gloucester, UK

Abstract

Background

Squamous cancer of the oesophagus occurs in certain regions of the world at up to a hundred times the incidence of others. A theory explaining the association has been put forward, involving a diet-based elevation of intragastric prostaglandin E2 (PGE2) production.

Method

We measured proliferation rates by MTT and BrdU assays of Het1A cells were measured following treatment with PGE2 and with 24 rural Transkeians gastric fluid samples. Changes in COX-2 expression and protein were measured by RT-PCR and ELISA, respectively, after PGE2 addition to the cell culture.

Results

We found that PGE2 was higher in gastric fluid samples from subjects on a high maize diet, than a varied diet. PGE2 increased cell proliferation rate as measured by BrdU assay by a factor of 14. Exposure of the cell line to gastric fluid samples increased cellular proliferation as measured by the MTT assay by a factor of 2 to 5. PGE2 increased COX-2 expression by over 25% for a majority of the treatments.

Conclusion

In oesophageal cells in vitro, we have shown that PGE2 causes increases in proliferation and expression of Cyclooxygenase 2 (COX 2), which in turn results in an imbalance of cellular proliferation, through a positive feedback mechanism pre-disposing the oesophagus to carcinoma.

Background

Squamous cancer of the oesophagus occurs in certain regions of the world at up to a hundred times the incidence of others. A theory explaining the association has been put forward, involving a diet-based elevation of intragastric prostaglandin E2 (PGE2) production.

Method

We measured proliferation rates by MTT and BrdU assays of Het1A cells were measured following treatment with PGE2 and with 24 rural Transkeians gastric fluid samples. Changes in COX-2 expression and protein were measured by RT-PCR and ELISA, respectively, after PGE2 addition to the cell culture.

Results

We found that PGE2 was higher in gastric fluid samples from subjects on a high maize diet, than a varied diet. PGE2 increased cell proliferation rate as measured by BrdU assay by a factor of 14. Exposure of the cell line to gastric fluid samples increased cellular proliferation as measured by the MTT assay by a factor of 2 to 5. PGE2 increased COX-2 expression by over 25% for a majority of the treatments.

Conclusion

In oesophageal cells in vitro, we have shown that PGE2 causes increases in proliferation and expression of Cyclooxygenase 2 (COX 2), which in turn results in an imbalance of cellular proliferation, through a positive feedback mechanism pre-disposing the oesophagus to carcinoma.

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