Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1982 Dec 1;95(3):734–741. doi: 10.1083/jcb.95.3.734

Biochemical analysis of secretory proteins synthesized by normal rat pancreas and by pancreatic acinar tumor cells

PMCID: PMC2112909  PMID: 6185502

Abstract

We have examined the secretogogue responsiveness and the pattern of secretory proteins produced by a transplantable rat pancreatic acinar cell tumor. Dispersed tumor cells were found to discharge secretory proteins in vitro when incubated with hormones that act on four different classes of receptors: carbamylcholine, caerulein, secretin- vasoactive intestinal peptide, and bombesin. With all hormones tested, maximal discharge from tumor cells was only about one-half that of control pancreatic lobules, but occurred at the same dose optima except for secretin, whose dose optimum was 10-fold higher. Biochemical analysis of secretory proteins discharged by the tumor cells was carried out by crossed immunoelectrophoresis and by two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoresis. To establish a baseline for comparison, secretory proteins from normal rat pancreas were identified according to enzymatic activity and correlated with migration position on two-dimensional gels. Our results indicate that a group of basic polypeptides including proelastase, basic trypsinogen, basic chymotrypsinogen, and ribonuclease, two out of three forms of procarboxypeptidase B, and the major lipase species were greatly reduced or absent in tumor cell secretion. In contrast, the amount of acidic chymotrypsinogen was notably increased compared with normal acinar cells. Although the acinar tumor cells are highly differentiated cytologically and express functional receptors for several classes of pancreatic secretagogues, they show quantitative and qualitative differences when compared with normal pancreas with regard to their production of secretory proteins.

Full Text

The Full Text of this article is available as a PDF (2.5 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amsterdam A., Jamieson J. D. Studies on dispersed pancreatic exocrine cells. I. Dissociation technique and morphologic characteristics of separated cells. J Cell Biol. 1974 Dec;63(3):1037–1056. doi: 10.1083/jcb.63.3.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BERNFELD P. Enzymes of starch degradation and synthesis. Adv Enzymol Relat Subj Biochem. 1951;12:379–428. doi: 10.1002/9780470122570.ch7. [DOI] [PubMed] [Google Scholar]
  3. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  4. Bradshaw W. S., Rutter W. J. Multiple pancreatic lipases. Tissue distribution and pattern of accumulation during embryological development. Biochemistry. 1972 Apr 11;11(8):1517–1528. doi: 10.1021/bi00758a029. [DOI] [PubMed] [Google Scholar]
  5. Dagorn J. C., Lahaie R. G. Dietary regulation of pancreatic protein synthesis. I. Rapid and specific modulation of enzyme synthesis by changes in dietary composition. Biochim Biophys Acta. 1981 Jun 26;654(1):111–118. doi: 10.1016/0005-2787(81)90142-8. [DOI] [PubMed] [Google Scholar]
  6. Genell S., Gustafsson B. E., Ohlsson K. Immunochemical quanitation of pancreatic endopeptidases in the intestinal contents of germfree and conventional rats. Scand J Gastroenterol. 1977;12(7):811–820. doi: 10.3109/00365527709181724. [DOI] [PubMed] [Google Scholar]
  7. Grant A. G., McGlashan D., Hermon-Taylor J. A study of pancreatic secretory and intracellular enzymes in pancreatic cancer tissue, other gastrointestinal cancers, normal pancreas and serum. Clin Chim Acta. 1978 Nov 15;90(1):75–82. doi: 10.1016/0009-8981(78)90086-4. [DOI] [PubMed] [Google Scholar]
  8. Iwanij V., Hull B. E., Jamieson J. D. Structural characterization of a rat acinar cell tumor. J Cell Biol. 1982 Dec;95(3):727–733. doi: 10.1083/jcb.95.3.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jamieson J. D., Ingber D. E., Muresan V., Hull B. E., Sarras M. P., Jr, Maylié-Pfenninger M. F., Iwanij V. Cell surface properties of normal, differentiating, and neoplastic pancreatic acinar cells. Cancer. 1981 Mar 15;47(6 Suppl):1516–1527. doi: 10.1002/1097-0142(19810315)47:6+<1516::aid-cncr2820471413>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  10. Jamieson J. D., Palade G. E. Synthesis, intracellular transport, and discharge of secretory proteins in stimulated pancreatic exocrine cells. J Cell Biol. 1971 Jul;50(1):135–158. doi: 10.1083/jcb.50.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KALNITSKY G., HUMMEL J. P., DIERKS C. [Some factors which affect the enzymatic digestion of ribonucleic acid]. J Biol Chem. 1959 Jun;234(6):1512–1516. [PubMed] [Google Scholar]
  12. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  13. Maylié-Pfenninger M. F., Jamieson J. D. Distribution of cell surface saccharides on pancreatic cells. II. Lectin-labeling patterns on mature guinea pig and rat pancreatic cells. J Cell Biol. 1979 Jan;80(1):77–95. doi: 10.1083/jcb.80.1.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Meldolesi J., Castiglioni G., Parma R., Nassivera N., De Camilli P. Ca++-dependent disassembly and reassembly of occluding junctions in guinea pig pancreatic acinar cells. Effect of drugs. J Cell Biol. 1978 Oct;79(1):156–172. doi: 10.1083/jcb.79.1.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pascale J., Avrameas S., Uriel J. The characterization of rat pancreatic zymogens and their active forms by gel diffusion techniques. J Biol Chem. 1966 Jul 10;241(13):3023–3027. [PubMed] [Google Scholar]
  16. Reboud J. P., Marchis-Mouren G., Paséro L., Cozzone A., Desnuelle P. Adaptation de la vitesse de biosynthèse DE L'amylase pancréatique et du chymotrypsinogène A des régimes riches en amidon ou en protéines. Biochim Biophys Acta. 1966 Apr 25;117(2):351–367. [PubMed] [Google Scholar]
  17. Reddy J. K., Reddy M. K., Hansen L. J., Qureshi S. A. Secretion granules of transplantable pancreatic acinar carcinoma of rat. Biochem J. 1980 Jun 15;188(3):921–924. doi: 10.1042/bj1880921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Robert B., Robert L. Determination of elastolytic activity with 125-I and 131-I labelled elastin. Eur J Biochem. 1969 Nov;11(1):62–67. doi: 10.1111/j.1432-1033.1969.tb00739.x. [DOI] [PubMed] [Google Scholar]
  19. Rohr G., Kern H., Scheele G. Enteropancreatic circulation of digestive enzymes does not exist in the rat. Nature. 1981 Jul 30;292(5822):470–472. doi: 10.1038/292470a0. [DOI] [PubMed] [Google Scholar]
  20. Scheele G. A. Human pancreatic cancer: analysis of proteins contained in pancreatic juice by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Cancer. 1981 Mar 15;47(6 Suppl):1513–1515. doi: 10.1002/1097-0142(19810315)47:6+<1513::aid-cncr2820471412>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  21. Scheele G. A., Palade G. E. Studies on the guinea pig pancreas. Parallel discharge of exocrine enzyme activities. J Biol Chem. 1975 Apr 10;250(7):2660–2670. [PubMed] [Google Scholar]
  22. Scheele G. A. Two-dimensional gel analysis of soluble proteins. Charaterization of guinea pig exocrine pancreatic proteins. J Biol Chem. 1975 Jul 25;250(14):5375–5385. [PubMed] [Google Scholar]
  23. Scheele G., Bartelt D., Bieger W. Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Gastroenterology. 1981 Mar;80(3):461–473. [PubMed] [Google Scholar]
  24. Schultz G. S., Sarras M. P., Jr, Gunther G. R., Hull B. E., Alicea H. A., Gorelick F. S., Jamieson J. D. Guinea pig pancreatic acini prepared with purified collagenase. Exp Cell Res. 1980 Nov;130(1):49–62. doi: 10.1016/0014-4827(80)90041-5. [DOI] [PubMed] [Google Scholar]
  25. Tartakoff A. M., Jamieson J. D., Scheele G. A., Palade G. E. Studies on the pancreas of the guinea pig. Parallel processing and discharge of exocrine proteins. J Biol Chem. 1975 Apr 10;250(7):2671–2677. [PubMed] [Google Scholar]
  26. Van Nest G. A., MacDonald R. J., Raman R. K., Rutter W. J. Proteins synthesized and secreted during rat pancreatic development. J Cell Biol. 1980 Sep;86(3):784–794. doi: 10.1083/jcb.86.3.784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Warren J. R., Reddy J. K. Transplantable pancreatic acinar carcinoma. Cancer. 1981 Mar 15;47(6 Suppl):1535–1542. doi: 10.1002/1097-0142(19810315)47:6+<1535::aid-cncr2820471416>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  28. Webb J. N. Acinar cell neoplasms of the exocrine pancreas. J Clin Pathol. 1977 Feb;30(2):103–112. doi: 10.1136/jcp.30.2.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zinterhofer L., Wardlaw S., Jatlow P., Seligson D. Nephelometric determination of pancreatic enzymes. II. Lipase. Clin Chim Acta. 1973 Mar 14;44(2):173–178. doi: 10.1016/0009-8981(73)90378-1. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES