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Enhanced Levels of Annexins in Pancreatic Carcinoma Cells of Syrian Hamsters and Their Intrapancreatic Allografts¹

Department of Biochemistry [K. D. K., J. K. V.] and Eppley Institute for Research in Cancer and Allied Diseases [M. H., P.M.P.], University of Nebraska Medical Center, Omaha, Nebraska 68198-4525

Annexins are a family of calcium- and phospholipid-binding proteins related by amino acid sequence homology. Annexins I and II are substrates for protein tyrosine kinases. Recent investigations have revealed a possible involvement of annexins I and II in mitogenic signal transduction and cell proliferation. To investigate further the involvement of annexins in cell proliferation, we measured the levels of annexins I and II and the enzyme 3-phosphoglycerate kinase (PGK) (annexin II and PGK are components of the primer recognition protein complex) in normal Syrian hamster pancreas, three hamster pancreatic ductal carcinoma cell lines, and allografts of the three cell lines into hamster pancreas. All three carcinoma cell lines had 5-8-fold higher levels of annexin II compared to normal pancreas. An inverse relationship was seen between level of annexin II and the doubling time of the cell culture. In intrapancreatic allografts, annexin II levels were 3-6-fold higher than in normal pancreas. Annexin I levels were 2-3-fold higher in the allografts. Significant increases (5-6-fold) in specific activity of PGK were seen in all allografts examined. However, the level of PGK, as measured by immunoblotting, was not significantly altered. Immunohistochemical staining revealed heterogeneity in the reactivity of the antiannexin and anti-PGK antibodies with tumor cells. Strikingly, the reactivity and staining intensity were greater in the proliferating regions of the primary tumors and in the metastatic foci. Mitotic cells were either unstained or very weakly stained. We conclude from these findings that annexin II and PGK, as primer recognition proteins, may have a role in cell proliferation.

¹ This study was supported by a grant to J. K. V. from the Nebraska Cancer and Smoking Diseases Program.

² To whom requests for reprints should be addressed, at the Department of Biochemistry, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-4525.

Received 7/24/91. Accepted 10/16/91.

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