Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents - PubMed (original) (raw)

Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents

Naoki Hashimoto. ISRN Gastroenterol. 2012.

Abstract

Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.

PubMed Disclaimer

Figures

Figure 1

Figure 1

EDA model: Esophagoduodenal anastomosis with total gastrectomy.

Figure 2

Figure 2

Macroscopic appearance of the esophagus in rats autopsied 40 weeks after surgery.

Figure 3

Figure 3

Microscopic findings in the distal portion of the esophagus in rats autopsied 40 weeks after surgery.

Figure 4

Figure 4

Immunohistochemical staining for COX2 in SCC and ADC.

Figure 5

Figure 5

Immunohistochemical staining for wild type p53 in SCC and ADC.

References

    1. Uys P, Van Helden PD. On the nature of genetic changes required for the development of esophageal cancer. Molecular Carcinogenesis. 2003;36(2):82–89. - PubMed
    1. Wijnhoven BPL, Tilanus HW, Dinjens WNM. Molecular biology of Barrett’s adenocarcinoma. Annals of Surgery. 2001;233(3):322–337. - PMC - PubMed
    1. Lagore C, Paraf F, Vidaud D, et al. COX2 is expressed frequently and early in Barrett’s esophagus and associated adenocacinoma. Histopathology. 2003;42:457–465. - PubMed
    1. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. The New England Journal of Medicine. 1999;340(11):825–831. - PubMed
    1. Kumagai H, Mukaisho KI, Sugihara H, Miwa K, Yamamoto G, Hattori T. Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats. Carcinogenesis. 2004;25(5):723–727. - PubMed

LinkOut - more resources