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Induction and Expression of Amphiregulin in Human Pancreatic Cancer¹

Division of Endocrinology and Metabolism, Departments of Medicine and Biological Chemistry, University of California, Irvine, California, 92717 [M. E., M. Y., M. S. K., M. E. L., M. K.]; Department of Visceral and Transplantation-Surgery, University of Berne, Inselspital, CH-3010 Berne, Switzerland [H. F., M. W. B.]; and Laboratory of Cell Biology, Division of Cytokine Biology, Food and Drug Administration, Bethesda, Maryland, 20892 [G. R. J.]

The epidermal growth factor receptor is activated by a family of polypeptides that includes the growth factor amphiregulin (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 . 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.

¹ This study was supported by Public Health Service Grant CA-40162 awarded by the NIH to M. K.

² Supported by Grant 2.93.43 awarded by the Gottlieb Daimler- und Karl Benz-Stiftung (Ladenburg, Germany) to M. E.

³ To whom requests for reprints should be addressed, at Division of Endocrinology and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92717.

Received 5/12/94. Accepted 6/14/94.

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