Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia

Gregory S. Ray, Jeffrey R. Lee, Kingsley Nwokeji, Luther R. Mills, James R. Goldenring

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Adenocarcinoma of the esophagus develops from metaplastic Barrett's columnar epithelia through the evolution of dysplastic epithelial intermediates. Although the role of dysplasia leading to adenocarcinoma is well established, far less is known regarding the cellular changes involved in this process. Because the development of dysplasia is characterized by the loss of apical secretory specializations, we hypothesized that changes in apical trafficking might be involved in the dysplastic process. We have sought to evaluate the expression of an important candidate regulator of apical trafficking, the small GTP-binding protein, Rab11, in resection and biopsy tissue from patients with Barrett's esophagus. Sections from esophageal resection specimens from 4 patients and endoscopic biopsies from 60 patients were stained with antibodies against Rab11 and Rab25 as well as protein markers of the Golgi apparatus and p53 protein. Rab11 staining in low-grade dysplastic regions was similar to that observed with monoclonal antibodies against Rab25 and γ-adaptin and colocalized with staining for the Golgi marker, the mannose-6-phosphate receptor. In the esophageal adenocarcinoma resections, prominent Rab11 immunostaining was observed in the supranuclear region of low-grade dysplastic cells. In contrast, regions of high-grade dysplasia demonstrating strong nuclear p53 staining showed only diffuse or absent Rab11 staining. In endoscopic biopsies, 91% of biopsies that were read unanimously as low-grade dysplasia demonstrated supranuclear Rab11 staining. Fourteen cement of biopsies unanimously graded as being without dysplasia demonstrated perinuclear Rab11 staining. No p53 immunostaining was observed in any of the low-grade dysplasia biopsy specimens. An increase in Rab11 immunoreactivity seems to correlate with low- grade dysplasia, whereas p53 immunostaining correlates with high-grade dysplasia. The colocalization of Rab11 staining with increased immunoreactivity for markers of the trans-Golgi system is consistent with a defect in apical trafficking due to an expansion of either the trans-Golgi compartment or the apical recycling vesicle system.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
JournalLaboratory Investigation
Volume77
Issue number5
StatePublished - Nov 1 1997

Fingerprint

Barrett Esophagus
GTP-Binding Proteins
Staining and Labeling
Biopsy
Adenocarcinoma
IGF Type 2 Receptor
Golgi Apparatus
Proteins
Monoclonal Antibodies
Antibodies

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Ray, G. S., Lee, J. R., Nwokeji, K., Mills, L. R., & Goldenring, J. R. (1997). Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia. Laboratory Investigation, 77(5), 503-511.

Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia. / Ray, Gregory S.; Lee, Jeffrey R.; Nwokeji, Kingsley; Mills, Luther R.; Goldenring, James R.

In: Laboratory Investigation, Vol. 77, No. 5, 01.11.1997, p. 503-511.

Research output: Contribution to journalArticle

Ray, GS, Lee, JR, Nwokeji, K, Mills, LR & Goldenring, JR 1997, 'Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia', Laboratory Investigation, vol. 77, no. 5, pp. 503-511.
Ray, Gregory S. ; Lee, Jeffrey R. ; Nwokeji, Kingsley ; Mills, Luther R. ; Goldenring, James R. / Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia. In: Laboratory Investigation. 1997 ; Vol. 77, No. 5. pp. 503-511.
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