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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 May;87(10):4012–4016. doi: 10.1073/pnas.87.10.4012

A cystic fibrosis pancreatic adenocarcinoma cell line.

R A Schoumacher 1, J Ram 1, M C Iannuzzi 1, N A Bradbury 1, R W Wallace 1, C T Hon 1, D R Kelly 1, S M Schmid 1, F B Gelder 1, T A Rado 1, et al.
PMCID: PMC54034  PMID: 1692630

Abstract

We established a pancreatic adenocarcinoma cell line (CFPAC-1) from a patient with cystic fibrosis (CF) and assessed some of its properties. The cells show epithelial morphology and express cytokeratin and oncofetal antigens characteristic of pancreatic duct cells. Basal and stimulated levels of cAMP and cAMP-dependent protein kinase and the biophysical properties of single Cl- channels in CFPAC-1 are similar to those of airway and sweat gland primary cultures and Cl(-)-secreting epithelial cell lines. Anion transport and single Cl- channel activity was stimulated by Ca2+ ionophores but not by forskolin, cAMP analogs, or phosphodiesterase inhibitors. The cells express the CF gene and manifest the most common CF mutation, deletion of three nucleotides resulting in a phenylalanine-508 deletion. These properties have been stable through greater than 80 passages (24 months), suggesting that CFPAC-1 can serve as a continuous cell line that displays the CF defect.

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Selected References

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  1. Barthelson R., Widdicombe J. Cyclic adenosine monophosphate-dependent kinase in cystic fibrosis tracheal epithelium. J Clin Invest. 1987 Dec;80(6):1799–1802. doi: 10.1172/JCI113274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. 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;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  3. Brinkley B. R., Fistel S. H., Marcum J. M., Pardue R. L. Microtubules in cultured cells; indirect immunofluorescent staining with tubulin antibody. Int Rev Cytol. 1980;63:59–95. doi: 10.1016/s0074-7696(08)61757-x. [DOI] [PubMed] [Google Scholar]
  4. Cheng H. C., Kemp B. E., Pearson R. B., Smith A. J., Misconi L., Van Patten S. M., Walsh D. A. A potent synthetic peptide inhibitor of the cAMP-dependent protein kinase. J Biol Chem. 1986 Jan 25;261(3):989–992. [PubMed] [Google Scholar]
  5. Clegg C. H., Correll L. A., Cadd G. G., McKnight G. S. Inhibition of intracellular cAMP-dependent protein kinase using mutant genes of the regulatory type I subunit. J Biol Chem. 1987 Sep 25;262(27):13111–13119. [PubMed] [Google Scholar]
  6. Fazekas de St Groth S. Automated production of monoclonal antibodies in a cytostat. J Immunol Methods. 1983 Feb 25;57(1-3):121–136. doi: 10.1016/0022-1759(83)90070-4. [DOI] [PubMed] [Google Scholar]
  7. Fogh J., Fogh J. M., Orfeo T. One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. J Natl Cancer Inst. 1977 Jul;59(1):221–226. doi: 10.1093/jnci/59.1.221. [DOI] [PubMed] [Google Scholar]
  8. Frizzell R. A., Rechkemmer G., Shoemaker R. L. Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science. 1986 Aug 1;233(4763):558–560. doi: 10.1126/science.2425436. [DOI] [PubMed] [Google Scholar]
  9. Gray M. A., Harris A., Coleman L., Greenwell J. R., Argent B. E. Two types of chloride channel on duct cells cultured from human fetal pancreas. Am J Physiol. 1989 Aug;257(2 Pt 1):C240–C251. doi: 10.1152/ajpcell.1989.257.2.C240. [DOI] [PubMed] [Google Scholar]
  10. Halm D. R., Rechkemmer G. R., Schoumacher R. A., Frizzell R. A. Apical membrane chloride channels in a colonic cell line activated by secretory agonists. Am J Physiol. 1988 Apr;254(4 Pt 1):C505–C511. doi: 10.1152/ajpcell.1988.254.4.C505. [DOI] [PubMed] [Google Scholar]
  11. Hayakawa T., Kondo T., Shibata T., Hamano H., Kitagawa M., Sakai Y., Ono H. Sensitive serum markers for detecting pancreatic cancer. Cancer. 1988 May 1;61(9):1827–1831. doi: 10.1002/1097-0142(19880501)61:9<1827::aid-cncr2820610918>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  12. Iannuzzi M. C., Dean M., Drumm M. L., Hidaka N., Cole J. L., Perry A., Stewart C., Gerrard B., Collins F. S. Isolation of additional polymorphic clones from the cystic fibrosis region, using chromosome jumping from D7S8. Am J Hum Genet. 1989 May;44(5):695–703. [PMC free article] [PubMed] [Google Scholar]
  13. Krouse M. E., Hagiwara G., Chen J., Lewiston N. J., Wine J. J. Ion channels in normal human and cystic fibrosis sweat gland cells. Am J Physiol. 1989 Jul;257(1 Pt 1):C129–C140. doi: 10.1152/ajpcell.1989.257.1.C129. [DOI] [PubMed] [Google Scholar]
  14. Landry D. W., Akabas M. H., Redhead C., Edelman A., Cragoe E. J., Jr, Al-Awqati Q. Purification and reconstitution of chloride channels from kidney and trachea. Science. 1989 Jun 23;244(4911):1469–1472. doi: 10.1126/science.2472007. [DOI] [PubMed] [Google Scholar]
  15. Lemna W. K., Feldman G. L., Kerem B., Fernbach S. D., Zevkovich E. P., O'Brien W. E., Riordan J. R., Collins F. S., Tsui L. C., Beaudet A. L. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis. N Engl J Med. 1990 Feb 1;322(5):291–296. doi: 10.1056/NEJM199002013220503. [DOI] [PubMed] [Google Scholar]
  16. Li M., McCann J. D., Liedtke C. M., Nairn A. C., Greengard P., Welsh M. J. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature. 1988 Jan 28;331(6154):358–360. doi: 10.1038/331358a0. [DOI] [PubMed] [Google Scholar]
  17. McIntosh J. C., Schoumacher R. A., Tiller R. E. Pancreatic adenocarcinoma in a patient with cystic fibrosis. Am J Med. 1988 Oct;85(4):592–592. doi: 10.1016/s0002-9343(88)80116-5. [DOI] [PubMed] [Google Scholar]
  18. Novak I., Greger R. Properties of the luminal membrane of isolated perfused rat pancreatic ducts. Effect of cyclic AMP and blockers of chloride transport. Pflugers Arch. 1988 May;411(5):546–553. doi: 10.1007/BF00582376. [DOI] [PubMed] [Google Scholar]
  19. Pinto V. B., Gelder F. B., Morris D. M. Purification, partial characterization, and clinical evaluation of an adenocarcinoma-associated antigen. Cancer Res. 1986 Dec;46(12 Pt 1):6520–6524. [PubMed] [Google Scholar]
  20. Rappolee D. A., Mark D., Banda M. J., Werb Z. Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping. Science. 1988 Aug 5;241(4866):708–712. doi: 10.1126/science.3041594. [DOI] [PubMed] [Google Scholar]
  21. Rommens J. M., Iannuzzi M. C., Kerem B., Drumm M. L., Melmer G., Dean M., Rozmahel R., Cole J. L., Kennedy D., Hidaka N. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. doi: 10.1126/science.2772657. [DOI] [PubMed] [Google Scholar]
  22. Schoumacher R. A., Shoemaker R. L., Halm D. R., Tallant E. A., Wallace R. W., Frizzell R. A. Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells. Nature. 1987 Dec 24;330(6150):752–754. doi: 10.1038/330752a0. [DOI] [PubMed] [Google Scholar]
  23. Smith P. L., Welsh M. J., Stoff J. S., Frizzell R. A. Chloride secretion by canine tracheal epithelium: I. Role of intracellular c AMP levels. J Membr Biol. 1982;70(3):217–226. doi: 10.1007/BF01870564. [DOI] [PubMed] [Google Scholar]
  24. Wallace D. H., Hegre O. D. Development in vitro of epithelial-cell monolayers derived from fetal rat pancreas. In Vitro. 1979 Apr;15(4):270–277. doi: 10.1007/BF02618951. [DOI] [PubMed] [Google Scholar]
  25. Wangemann P., Wittner M., Di Stefano A., Englert H. C., Lang H. J., Schlatter E., Greger R. Cl(-)-channel blockers in the thick ascending limb of the loop of Henle. Structure activity relationship. Pflugers Arch. 1986;407 (Suppl 2):S128–S141. doi: 10.1007/BF00584942. [DOI] [PubMed] [Google Scholar]
  26. Welsh M. J., Liedtke C. M. Chloride and potassium channels in cystic fibrosis airway epithelia. 1986 Jul 31-Aug 6Nature. 322(6078):467–470. doi: 10.1038/322467a0. [DOI] [PubMed] [Google Scholar]

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