Expression of Reg Iα Protein in Human Gastric Cancers

Abstract

Background/Aims: Although regeneratinggene(Reg) Iα protein has a trophic effect on gastric epithelial cells, it is unclear whether Reg Iα protein and its receptor are involved in gastric carcinogenesis. Therefore, we investigated the Reg Iα protein expression in human gastric cancers and assessed its relationship to clinicopathological factors. Methods: Sixty-one gastric cancer specimens were examined, using immunohistochemistry, for Reg Iα protein, p53, and proliferating cell nuclear antigen. The expression of both Reg Iα and Reg receptor mRNA was examined in seven human gastric cancer cell lines (MKN1, MKN28, MKN45, MKN74, KATOIII, GCIY, and AGS) by reverse transcription-polymerase chain reaction and Northern blot analysis. Results: Twenty-three (37.7%) of the 61 gastric cancer tissues samples were positive for Reg Iα protein. The Reg Iα expression was significantly related to the presence of lymphatic invasion but not to tumor size, tumor stage, Lauren’s classification, presence of venous invasion, lymph node metastases, or p53 overexpression. Gastric cancers positive for Reg Iα protein showed a significantly higher proliferating cell nuclear antigen labeling index than negative ones. The expression of both Reg Iα and Reg receptor mRNA was detected in all seven gastric cancer cell lines. Conclusion: Reg Iα protein may play a role in the development of gastric cancers.

Expression profile of REG family proteins REG Iα and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers

“…19 At present, REG family proteins are classified into four subfamilies according to their primary structures, 20 and their overexpression has been reported in neoplastic or inflamed tissues in various organs including the stomach, colorectum, bile duct, and pancreas. [5][6][7][8]14,21,22 Interestingly, microarray analyses suggest that expression of the REG Ia and REG IV genes is prominently upregulated during the development of gastric cancer, 10,11 and in fact we found immunohistochemically that not only REG Ia but also REG IV protein was overexpressed in a considerable number of gastric cancers. However, we also found that REG Ia and REG IV were not always coexpressed in a subset of gastric cancers.…”

“…5 In brief, 4-mm-thick sections were placed on slides, deparaffinized, and dehydrated. They were then placed in 0.01 mol/l citrate buffer (pH 6.0) and treated by microwave heating (MI-77; Azumaya, Tokyo, Japan; 400 W, 951C) for 10 and 40 min to facilitate antigen retrieval for REG Ia and Ki-67, respectively, whereas they received no treatment with microwave heating for the immunostaining of ssDNA.…”

“…4 Among human REG family proteins, REG Ia and REG IV are reportedly overexpressed in a subset of gastric cancer. [5][6][7][8][9] Moreover, several microarray analyses have recently isolated REG Ia and REG IV as novel genes that are overexpressed in gastric cancer tissues, 10,11 suggesting that both genes have important functions in gastric carcinogenesis. Indeed, we have previously clarified that REG Ia acts as a trophic and/or anti-apoptotic factor in the development of gastric cancer, 12 and others have reported that REG IV protein confers cell resistance to chemotherapeutic agents, 9 suggesting that these proteins are both associated with tumor progression.…”

“…Indeed, we have previously clarified that REG Ia acts as a trophic and/or anti-apoptotic factor in the development of gastric cancer, 12 and others have reported that REG IV protein confers cell resistance to chemotherapeutic agents, 9 suggesting that these proteins are both associated with tumor progression. It is noteworthy that in non-neoplastic tissues REG Ia and REG IV are commonly expressed not only in endocrine cells but also in metaplastic cells that frequently accompany gastric cancer lesions, 5,8,12,13 implying a possible link between REG protein expression and mucin phenotype of gastric lesions. In addition, there is increasing speculation as to whether REG Ia and REG IV protein expression may be applicable as a prognostic marker for patients with various malignancies.…”

Involvement of the IL-22/REG Iα axis in ulcerative colitis

“…1 Thereafter, its human homologue REG Ia protein was suggested to be involved in the pathophysiology of gastrointestinal inflammation and its associated cancer. [2][3][4][5][6] Indeed, we previously reported that REG Ia protein behaves as a trophic and/or an anti-apoptotic factor in the development of colitis-or gastritis-associated cancer. 5,6 To clarify the regulatory mechanism of REG Ia gene expression, we initially screened major cytokines and showed that interleukin (IL)-6 and IFN-g are possible stimulators of REG Ia gene expression under inflammatory conditions.…”