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Induction and expression of amphiregulin in human pancreatic cancer
M Ebert1, M Yokoyama, M S Kobrin
1Department of Medicine, University of California, Irvine 92717.
Abstract:
The epidermal growth factor receptor is activated by a family of polypeptides that includes the growth factor amphiregullin (AR). Using Northern blot analysis and the polymerase chain reaction, we now report that AR mRNA is expressed in human pancreatic cancer cell lines, and that this expression is enhanced in several of these cell lines by tetradecanoyl phorbol acetate and transforming growth factor alpha. AR was also expressed in normal and malignant pancreatic tissues. However, in the normal pancreas, AR immunostaining was most evident in the nuclei of ductal cells. In contrast, in many carcinomas, AR was also present in the cytoplasm of the ductal-like cancer cells. Cytoplasmic localization of AR was associated with a more advanced clinical stage. These findings suggest that AR may contribute to aberrant activation of the epidermal growth factor receptor in human pancreatic cancer, and may enhance disease progression.
Insights
Amphiregulin (AR) mRNA is found in human pancreatic cancer cells and tissues. Its cytoplasmic localization in cancer cells correlates with advanced disease, suggesting a role in pancreatic cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Epidermal growth factor receptor (EGFR) signaling is crucial in cell growth and differentiation.
- Aberrant EGFR activation is implicated in various cancers, including pancreatic cancer.
- Amphiregulin (AR) is a polypeptide that activates EGFR.
Purpose of the Study:
- To investigate the expression and localization of Amphiregulin (AR) in human pancreatic cancer.
- To determine the correlation between AR expression/localization and pancreatic cancer progression.
Main Methods:
- Northern blot analysis to detect AR mRNA expression.
- Polymerase chain reaction (PCR) to quantify AR mRNA levels.
- Immunohistochemistry to assess AR protein localization in pancreatic tissues.
Main Results:
- AR mRNA is expressed in human pancreatic cancer cell lines and tissues.
- AR expression is enhanced by tetradecanoyl phorbol acetate and transforming growth factor alpha in some cell lines.
- In normal pancreas, AR is mainly in ductal cell nuclei; in carcinomas, it is also found in the cytoplasm.
- Cytoplasmic AR localization is associated with more advanced clinical stages of pancreatic cancer.
Conclusions:
- Amphiregulin (AR) is expressed in human pancreatic cancer.
- AR's cytoplasmic localization in cancer cells may contribute to aberrant EGFR activation.
- AR may play a role in the progression of pancreatic cancer.
