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Medical Oncology

, 32:265 | Cite as

Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis

  • Ting-Zi Hu
  • Li-Hua Huang
  • Can-Xia XuEmail author
  • Xiao-Ming Liu
  • Yu Wang
  • Jing Xiao
  • Li Zhou
  • Ling Luo
  • Xiao-Xia Jiang
Original Paper

Abstract

Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPα were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma.

Keywords

Transcription factors Helicobacter pylori Gastric carcinogenesis Protein/DNA array analysis AP4 Pbx1 C/EBPα 

Abbreviations

H. pylori

Helicobacter pylori

TFs

Transcription factors

NGM

Normal gastric mucosa

NAG

Non-atrophic gastritis

CAG

Chronic atrophic gastritis

IM

Intestinal metaplasia

DYS

Dysplasia

PLGC

Precancerous lesions of gastric cancer

GC

Gastric carcinoma

CagA

Cytotoxin-associated gene A

VacA

Vacuolating cytotoxin gene A

GATA-3

GATA-binding protein 3

AP4

Activator protein 4 binding element

Pbx1

Pre-B-cell leukemia transcription factor 1

C/EBP α

CCAAT/enhancer-binding protein α

CCAAT-BP

CCAAT-binding protein

CACC-BP

CACC-binding protein

Notes

Acknowledgments

This study is supported by a Grant from the National Natural Science Foundation of China (No. 81172301).

Author contributions

Hu T analyzed the data and wrote the manuscript; Huang L guided the analysis and manuscript writing; Xu CX designed the study, performed the endoscopic procedures, collected specimens and revised the manuscript; Liu X, Xiao J and Zhou L conducted the cell and Helicobacter pylori experiments; Wang Y collected and sent the specimens for array analysis; Luo L and Jiang X performed the experiment of Mongolian gerbils.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

12032_2015_711_MOESM1_ESM.docx (21 kb)
Supplementary material 1 (DOCX 21 kb)
12032_2015_711_MOESM2_ESM.docx (17 kb)
Supplementary material 2 (DOCX 16 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ting-Zi Hu
    • 1
  • Li-Hua Huang
    • 2
  • Can-Xia Xu
    • 1
    • 4
    Email author
  • Xiao-Ming Liu
    • 1
  • Yu Wang
    • 3
  • Jing Xiao
    • 1
  • Li Zhou
    • 1
  • Ling Luo
    • 1
  • Xiao-Xia Jiang
    • 1
  1. 1.Department of GastroenterologyThird Xiangya Hospital of Central South UniversityChangshaChina
  2. 2.Center for Medical ExperimentThird Xiangya Hospital, Central South UniversityChangshaChina
  3. 3.Department of Internal MedicineThe Third People’s Hospital of HuaihuaHuaihuaChina
  4. 4.Hunan Key Laboratory of Nonresolving Inflammation and CancerChangshaChina

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