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The role of Reg IV gene and its encoding product in gastric carcinogenesis

Hua-Chuan Zheng1, Xiao-Yan Xu, Miao Yu

  • 1Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, 110001 China. zheng_huachuan@hotmail.com

Human Pathology
|September 11, 2009
PubMed

Insights

Regenerating Isotype 4 (Reg IV) protein expression increases in early gastric precancerous lesions like intestinal metaplasia and adenoma, then decreases in gastric cancer. Elevated serum Reg IV may indicate gastric cancer.

Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Regenerating Isotype 4 (Reg IV) is implicated in colon cancer, activating signaling pathways and inhibiting apoptosis.
  • Its precise role in gastric carcinogenesis remains unclear.

Purpose of the Study:

  • To investigate the expression and role of Reg IV in gastric carcinogenesis and progression.
  • To evaluate Reg IV as a potential biomarker for gastric precancerous lesions.

Main Methods:

  • Immunohistochemistry and in situ hybridization on tissue microarrays of gastric tissues (carcinoma, nonneoplastic mucosa, adenoma, intestinal metaplasia, gastritis).
  • Western blot and RT-PCR analysis of gastric cancer cell lines and tissue samples.
  • Enzyme-linked immunosorbent assay (ELISA) for serum Reg IV levels.
  • Correlation analysis with MUC-2 and MUC-5AC expression and WHO histologic subtypes.

Main Results:

  • Reg IV protein expression decreased progressively from intestinal metaplasia/adenoma to gastric carcinoma and gastritis.
  • Reg IV mRNA levels were higher in intestinal metaplasia compared to carcinoma or nonneoplastic mucosa.
  • Elevated serum Reg IV levels were observed in gastric carcinoma patients versus healthy individuals.
  • Reg IV expression correlated with MUC-2 and MUC-5AC, and was higher in signet ring cell carcinoma.

Conclusions:

  • Reg IV expression is upregulated in gastric intestinal metaplasia and adenoma, then downregulated during malignant transformation.
  • Reg IV serves as a potential biomarker for gastric precancerous lesions.
  • Reg IV expression is linked to the histogenic pathway of signet ring cell carcinoma.

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