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Epidermal growth factor (EGF/URO) induces expression of regulatory peptides in damaged human gastrointestinal tissues
N A Wright1, R Poulsom, G W Stamp
1Imperial Cancer Research Fund Histopathology Unit, London, U.K.
Abstract:
The pS2 gene encodes for a small cysteine-rich protein, and was originally found by differential screening of a cDNA library from the human breast carcinoma cell line, MCF-7. The presence of pS2 is closely correlated with oestrogen dependence in breast carcinomas. While the function of pS2 is unknown, pS2 protein has been shown to be homologous with the gastrointestinal peptide hormone pancreatic spasmolytic polypeptide (PSP) and its human counterpart hSP, in which a 5-cysteine domain is tandemly repeated. The 5' flanking region of the pS2 gene contains an enhancer region responsive to oestrogens and to epidermal growth factor (EGF/URO). We now report that pS2 and hSP expression occurs in a wide range of endodermally-derived tissues, including the duodenum, the pancreas, and in a recently defined cell lineage associated with chronic gastrointestinal ulceration. In each case, this expression was associated with secretion of immunoreactive EGF/URO. We further show that the co-expression of pS2 and hSP in gastric surface epithelial cells is also associated with the secretion of EGF/URO in the subjacent mucous neck cells. Our results indicate that local EGF/URO secretion induces pS2 and hSP in adjacent cells, and that these molecules are then available to participate in pathophysiological responses. The finding of similar patterns of EGF/URO, hSP and pS2 expression in association with chronic damage suggests that this is a fundamental response in the healing of these tissues.
Insights
The pS2 gene and human stomach peptide (hSP) are expressed in gastrointestinal tissues, particularly during healing. Epidermal growth factor (EGF/URO) secretion appears to trigger this response in adjacent cells.
Area of Science:
- Molecular Biology
- Gastroenterology
- Oncology
Background:
- The pS2 gene, identified in breast cancer cells, encodes a protein homologous to pancreatic spasmolytic polypeptide (PSP) and human stomach peptide (hSP).
- pS2 expression correlates with estrogen dependence in breast carcinomas, and its function remains largely unknown.
- The pS2 gene's regulatory region contains elements responsive to estrogens and epidermal growth factor (EGF/URO).
Purpose of the Study:
- To investigate the expression patterns of pS2 and hSP in various endodermally-derived tissues.
- To determine the relationship between pS2/hSP expression and epidermal growth factor (EGF/URO) secretion.
- To explore the role of pS2, hSP, and EGF/URO in tissue repair and pathophysiological responses.
Main Methods:
- Differential screening of cDNA libraries.
- Immunohistochemical analysis of tissue expression.
- Detection of immunoreactive EGF/URO.
Main Results:
- pS2 and hSP expression were observed in diverse endodermally-derived tissues, including the duodenum, pancreas, and tissues associated with gastrointestinal ulceration.
- Expression of pS2 and hSP consistently correlated with the secretion of immunoreactive EGF/URO.
- Co-expression of pS2 and hSP in gastric surface epithelial cells was linked to EGF/URO secretion in underlying mucous neck cells.
Conclusions:
- Local EGF/URO secretion induces pS2 and hSP expression in adjacent cells, suggesting a coordinated cellular response.
- These molecules may play a role in pathophysiological processes within the gastrointestinal tract.
- The co-occurrence of EGF/URO, hSP, and pS2 expression in damaged tissues indicates a fundamental role in tissue healing and repair.