ABCG2/V-ATPase was associated with the drug resistance and tumor metastasis of esophageal squamous cancer cells

Diagn Pathol. 2012 Dec 17:7:180. doi: 10.1186/1746-1596-7-180.

Abstract

Background: ATP-binding cassette sub-family G member 2 (ABCG2) is a protein that in humans is encoded by the ABCG2 gene. ABCG2 participates in efflux of many chemotherapeutic agents. ABCG2 is often expressed in hematopoietic progenitor or stem cells. Vacuolar-H + -ATPase (V-ATPase) plays a key role in adjusting and maintaining intracellular pH and in regulating the drug tolerance of cells. The TNM Classification of Malignant Tumours (TNM) is a cancer staging system that describes the extent of cancer in a patient's body. In this study, the expression of ABCG2 and V-ATPase in esophageal squamous cancer cells was detected.

Methods: Immunohistochemistry staining and Immunofluorescence double staining were used to detect the expression of ABCG2 and V-ATPase in in 66 cases of esophageal squamous cancer cells. Associations and differences in expression of ABCG2 with that of V-ATPase were analyzed.

Results: Positive staining patterns for both ABCG2 (66.67%) and V-ATPase (68.18%) were located mainly in the plasma membrane and cytoplasm. Marked differences in expression were also shown (P < 0.001) among 3 groups of pathological grades and TNM stages in these carcinomas. Marked differences were also found for ABCG2 expression between the two groups in the pathological grades and in the TNM staging groups (P < 0.01), but not between the αb and βgroups. V-ATPase expression was statistically significant between the 2 groups in the pathological grades and TNM stages (P < 0.05). This was not evident between α and β groups of pathological grades or between αb and βof the TNM stages. Marked differences in expression of ABCG2 and V-ATPase were found between metastatic and non-metastatic groups in the same carcinomas (P < 0.0001). There was also a clear correlation between the expression of ABCG2 and V-ATPase (P ≤ 0.001) in the various groups of pathological grades and TNM stages.

Conclusions: Both ABCG2 and V-ATPase were over-expressed in esophageal squamous cancer cells. Their expression was associated with pathological grade, TNM stage and tumor metastasis in esophageal squamous cancer cells, suggesting interaction relationship between them. ABCG2 and V-ATPase expression may be strongly associated with drug resistance and tumor metastasis.

Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3823783918433897.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / analysis*
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / secondary
  • Cell Membrane / enzymology
  • Cytoplasm / enzymology
  • Drug Resistance, Neoplasm*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / analysis*
  • Neoplasm Staging
  • Prognosis
  • Up-Regulation
  • Vacuolar Proton-Translocating ATPases / analysis*

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Biomarkers, Tumor
  • Neoplasm Proteins
  • Vacuolar Proton-Translocating ATPases