Identification of Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI-2)-Related Small Peptide (H2RSP): Its Nuclear Localization and Generation of Chimeric mRNA Transcribed from both HAI-2 and H2RSP Genes

Itoh, Hiroshi; Kataoka, Hiroaki; Yamauchi, Masamichi; Naganuma, Seiji; Akiyama, Yutaka; Nuki, Yoshitsugu; Shimomura, Takeshi; Miyazawa, Keiji; Kitamura, Naomi; Koono, Masashi

doi:10.1006/bbrc.2001.5767

Cited by 6 publications

(12 citation statements)

References 23 publications

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“…H2RSP may not be expressed in the intestinal tissue as a chimeric form with HAI-2, 15 because this transcript was not detected in the gastrointestinal mucosa. 18 Therefore, the intestinal expression of H2RSP is not linked to the activation of hepatocyte growth factor and the subsequent MET signalling pathway, both of which have important roles in the proliferation and differentiation of gastrointestinal mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…19 A 352-bp cDNA fragment corresponding to bases 88-439 of the human H2RSP cDNA sequence 15 was used as a template to generate digoxigenin-labelled probes. The same amount of each antisense or sense probe (1 ng/slide) was used.…”

Section: Antibodiesmentioning

confidence: 99%

“…The expression levels were verified by northern blot or RT-PCR. 15 F (6 clones), FY (5 clones), Y (6 clones) and mock (2 clones) were isolated using CHO cells, and two clones of each were selected for subsequent study. A clone of DLD-1 overexpressing H2RSP was also prepared.…”

Section: Establishment Of H2rsp-expressing Cells and Their Growth Chamentioning

confidence: 99%

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Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers

Uchiyama

Itoh²,

Naganuma³

et al. 2007

Gut

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Background: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. Aims: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. Methods: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. Results: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear b-catenin. The number of H2RSP-positive cells in the invasive front of welldifferentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. Conclusion: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Antibodiesmentioning

confidence: 99%

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Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers

Uchiyama

Itoh²,

Naganuma³

et al. 2007

Gut

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“…The H2RSP gene was first described in 2001 by Itoh et al (Itoh et al, 2001), who observed H2RSP expression in tissues obtained from the gastrointestinal tract. H2RSP protein, which is identical to immortalization-upregulated protein (IMUP-1), is a small protein constituting 106 amino acids.…”

Section: Hepatocyte Growth Factor Activator Inhibitor Type 2-related mentioning

confidence: 99%

Molecular Traits of the Budding Colorectal Cancer Cells

Nielsen¹

2012

Colorectal Cancer Biology - From Genes to Tumor

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“…Hepatocyte growth factor (HGF) activator inhibitor type 2 (HAI-2)-related small peptide (H2RSP) is a small nuclear peptide recently identified during the search for splicing variant forms of human HAI-2 [3]. HAI-2 is a Kunitz-type serine proteinase inhibitor that regulates the activity of HGF activator (HGFA), a serine proteinase responsible for proteolytic processing of immature single-chain HGF into mature two-chain HGF [2,5,6].…”

Section: Introductionmentioning

confidence: 99%

Nuclear translocation of H2RSP is impaired in regenerating intestinal epithelial cells of murine colitis model

et al. 2005

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Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a recently identified nuclear peptide that is abundantly expressed in the gastrointestinal tract. In this study, we analyzed the expression of H2RSP in normal and injured intestinal mucosa in a murine experimental colitis induced by oral administration of 2.5% dextran sodium sulfate. Results of immunohistochemistry and in situ hybridization showed that H2RSP was expressed predominantly in the epithelium of normal intestine. Whereas H2RSP was localized in the cytoplasm of cells in the crypt, it was translocated into the nuclei of the surface epithelial cells. In injured intestine, H2RSP was detected in the cytoplasm of regenerating epithelial cells, and the nuclear translocation was impaired even in the surface epithelium. However, the mRNA level was not significantly altered in these cells by real-time reverse transcription-polymerase chain reaction using total RNAs obtained from the fractionated mucosal tissue samples prepared by laser-captured microdissection technique. On the other hand, H2RSP mRNA was significantly upregulated in the stromal cells of injured intestinal mucosa compared with those in normal mucosa, which shows cytoplasmic localization of H2RSP. These circumstantial evidences suggest that the nuclear translocation of H2RSP may be related to a signaling involved in the transition from cellular proliferation to differentiation.

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Identification of Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI-2)-Related Small Peptide (H2RSP): Its Nuclear Localization and Generation of Chimeric mRNA Transcribed from both HAI-2 and H2RSP Genes

Cited by 6 publications

References 23 publications

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers

Molecular Traits of the Budding Colorectal Cancer Cells

Nuclear translocation of H2RSP is impaired in regenerating intestinal epithelial cells of murine colitis model

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