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PMID: 8977340 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes.

Gut ·Vol. 39 ·No. 2 ·1996-08-00 ·Pages 255-61

Rosewicz S, Weder M, Kaiser A, Riecken EO

Abstract

The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood. To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines. The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies. Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2. Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.

MeSH Terms
Blotting, Western Carcinoma, Ductal, Breast/enzymology Cell Division Electrophoresis Humans Interferon-alpha/pharmacology Isoenzymes/antagonists & inhibitors,drug effects Pancreatic Neoplasms/enzymology Polymerase Chain Reaction Protein Kinase C/antagonists & inhibitors,drug effects Tumor Cells, Cultured/cytology,drug effects,enzymology
Chemicals
Interferon-alpha Isoenzymes Protein Kinase C
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Rosewicz S
Department of Gastroenterology, Medizinische Klinik and Poliklinik, Khnikum Benjamin Franklin, Berlin, Germany.
Weder M
Kaiser A
Riecken E O
References (32)
32 references, click to expand
  1. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.
    Science. 1992 Oct 23;258(5082):607-14 PMID: 1411571
  2. Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial.
    Scand J Gastroenterol. 1992 Apr;27(4):317-25 PMID: 1589710
  3. Protein kinase C isoenzymes: divergence in signal transduction?
    Biochem J. 1993 Apr 15;291 ( Pt 2):329-43 PMID: 8484714
  4. Cell cycle-dependent modulation of alpha-interferon-inducible gene expression and activation of signaling components in Daudi cells.
    J Biol Chem. 1994 Oct 14;269(41):25437-41 PMID: 7929242
  5. Retinoids: effects on growth, differentiation, and nuclear receptor expression in human pancreatic carcinoma cell lines.
    Gastroenterology. 1995 Nov;109(5):1646-60 PMID: 7557150
  6. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  7. The molecular heterogeneity of protein kinase C and its implications for cellular regulation.
    Nature. 1988 Aug 25;334(6184):661-5 PMID: 3045562
  8. Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells.
    Blood. 1989 Jan;73(1):123-30 PMID: 2783371
  9. The protein kinase C family: heterogeneity and its implications.
    Annu Rev Biochem. 1989;58:31-44 PMID: 2549852
  10. Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth.
    Cancer Res. 1990 Jan 1;50(1):103-7 PMID: 2152769
  11. Cancer statistics, 1990.
    CA Cancer J Clin. 1990 Jan-Feb;40(1):9-26 PMID: 2104569
  12. Genetic transfer of a functional human interferon alpha receptor into mouse cells: cloning and expression of its cDNA.
    Cell. 1990 Jan 26;60(2):225-34 PMID: 2153461
  13. Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental and human malignancies: a review.
    Cancer Res. 1990 Jun 15;50(12):3473-86 PMID: 1692761
  14. Overexpression of protein kinase C alpha-subtype in Swiss/3T3 fibroblasts causes loss of both high and low affinity receptor numbers for epidermal growth factor.
    J Biol Chem. 1990 Aug 5;265(22):13290-6 PMID: 1695906
  15. Interferon-alpha selectively activates the beta isoform of protein kinase C through phosphatidylcholine hydrolysis.
    Proc Natl Acad Sci U S A. 1990 Sep;87(17):6537-41 PMID: 2168551
  16. Possible role of Ca2(+)-independent protein kinase C isozyme, nPKC epsilon, in thyrotropin-releasing hormone-stimulated signal transduction: differential down-regulation of nPKC epsilon in GH4C1 cells.
    Biochem Biophys Res Commun. 1990 Oct 15;172(1):184-9 PMID: 2171516
  17. Protein kinase C gamma expression mimics phorbol ester-induced transcriptional activation of a murine VL30 enhancer element.
    Cell Growth Differ. 1991 Jan;2(1):7-14 PMID: 2007096
  18. Chemotherapy for pancreatic cancer.
    Baillieres Clin Gastroenterol. 1990 Dec;4(4):953-68 PMID: 2078794
  19. The priming effect of human interferon-alpha is mediated by protein kinase C.
    J Interferon Res. 1990 Dec;10(6):589-97 PMID: 1964949
  20. Protein kinase C is involved in the early signals of interferon-alpha but not of interferon-gamma in U937 cells.
    J Interferon Res. 1990 Dec;10(6):605-11 PMID: 2128303
  21. A rapid micropreparation technique for extraction of DNA-binding proteins from limiting numbers of mammalian cells.
    Nucleic Acids Res. 1991 May 11;19(9):2499 PMID: 2041787
  22. Transmembrane signaling by interferon alpha involves diacylglycerol production and activation of the epsilon isoform of protein kinase C in Daudi cells.
    Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):7988-92 PMID: 1832772
  23. Inhibition of erythropoietin production by phorbol ester is associated with down-regulation of protein kinase C-alpha isoenzyme in hepatoma cells.
    Biochem Biophys Res Commun. 1991 Sep 30;179(3):1441-8 PMID: 1656952
  24. Antitumour effects of interferons: past, present and future.
    Br J Haematol. 1991 Oct;79 Suppl 1:1-5 PMID: 1718388
  25. Rational basis for the metabolic modulation of 5-fluorouracil by leucovorin and interferon alpha.
    Br J Haematol. 1991 Oct;79 Suppl 1:52-5 PMID: 1931710
  26. Protein kinase activity required for an early step in interferon-alpha signaling.
    J Biol Chem. 1991 Dec 5;266(34):23471-6 PMID: 1744140
  27. Protein kinase C.
    Pharmacol Ther. 1991;51(1):71-95 PMID: 1771178
  28. The interferon system. A bird's eye view of its biochemistry.
    J Biol Chem. 1992 Mar 15;267(8):5017-20 PMID: 1371992
  29. Intermediate filaments as differentiation markers of normal pancreas and pancreas cancer.
    Am J Pathol. 1992 Mar;140(3):559-68 PMID: 1372155
  30. Biochemical modulation of 5-fluorouracil by folinic acid or alpha-interferon with and without other cytostatic drugs in gastric, esophageal, and pancreatic cancer.
    Semin Oncol. 1992 Apr;19(2 Suppl 3):215-9 PMID: 1557651
  31. Expression pattern of alpha-protein kinase C in human astrocytomas indicates a role in malignant progression.
    Cancer Res. 1992 May 15;52(10):2951-6 PMID: 1316231
  32. Inhibition of human pancreatic cancer cell (MIA PaCa-2) growth by cholera toxin and 8-chloro-cAMP in vitro.
    Br J Cancer. 1993 Feb;67(2):279-83 PMID: 8381655
Article Info
Journal
Gut
Abbr.
Gut
ISSN
0017-5749
Published
1996-08-00
Pages
255-61
Language
English
Region
England
NLM ID
2985108R
PMCID
PMC1383308
Subset
IM
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