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British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Aug;70(2):244–247. doi: 10.1038/bjc.1994.287

Proliferating cell nuclear antigen expression in non-cycling cells may be induced by growth factors in vivo.

P A Hall 1, P J Coates 1, R A Goodlad 1, I R Hart 1, D P lane 1
PMCID: PMC2033489  PMID: 7914422

Abstract

The proliferating cell nuclear antigen (PCNA) is required for DNA replication and DNA nucleotide excision repair. Considerable evidence points to PCNA expression being a marker of proliferation in many situations. However, while levels of PCNA are normally very low in non-cycling tissues, high levels of the protein have been observed in the normal tissues surrounding human breast and pancreatic tumours. Using two model systems we have shown that PCNA is induced in non-cycling cells by adjacent transplanted tumour cells and that this phenomenon may be mimicked by the in vivo administration of growth factors (transforming growth factor alpha and epidermal growth factor). These data suggest that tumours may elaborate factors that induce PCNA expression in nearby normal cells. PCNA induction the normal cells surrounding tumours is a direct example of the effect of tumour cells on normal surrounding tissues. This effect may prove to be a useful parameter in the analysis of tumour-host interactions.

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Selected References

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  1. Anzano M. A., Rieman D., Prichett W., Bowen-Pope D. F., Greig R. Growth factor production by human colon carcinoma cell lines. Cancer Res. 1989 Jun 1;49(11):2898–2904. [PubMed] [Google Scholar]
  2. Barton C. M., Hall P. A., Hughes C. M., Gullick W. J., Lemoine N. R. Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol. 1991 Feb;163(2):111–116. doi: 10.1002/path.1711630206. [DOI] [PubMed] [Google Scholar]
  3. Baserga R. Growth regulation of the PCNA gene. J Cell Sci. 1991 Apr;98(Pt 4):433–436. doi: 10.1242/jcs.98.4.433. [DOI] [PubMed] [Google Scholar]
  4. Bravo R., Frank R., Blundell P. A., Macdonald-Bravo H. Cyclin/PCNA is the auxiliary protein of DNA polymerase-delta. Nature. 1987 Apr 2;326(6112):515–517. doi: 10.1038/326515a0. [DOI] [PubMed] [Google Scholar]
  5. Bravo R., Macdonald-Bravo H. Existence of two populations of cyclin/proliferating cell nuclear antigen during the cell cycle: association with DNA replication sites. J Cell Biol. 1987 Oct;105(4):1549–1554. doi: 10.1083/jcb.105.4.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Celis J. E., Madsen P. Increased nuclear cyclin/PCNA antigen staining of non S-phase transformed human amnion cells engaged in nucleotide excision DNA repair. FEBS Lett. 1986 Dec 15;209(2):277–283. doi: 10.1016/0014-5793(86)81127-9. [DOI] [PubMed] [Google Scholar]
  7. Chang C. D., Ottavio L., Travali S., Lipson K. E., Baserga R. Transcriptional and posttranscriptional regulation of the proliferating cell nuclear antigen gene. Mol Cell Biol. 1990 Jul;10(7):3289–3296. doi: 10.1128/mcb.10.7.3289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goodlad R. A., Lee C. Y., Wright N. A. Cell proliferation in the small intestine and colon of intravenously fed rats: effects of urogastrone-epidermal growth factor. Cell Prolif. 1992 Sep;25(5):393–404. doi: 10.1111/j.1365-2184.1992.tb01449.x. [DOI] [PubMed] [Google Scholar]
  9. Goodlad R. A., Wilson T. J., Lenton W., Gregory H., McCullagh K. G., Wright N. A. Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats. Gut. 1987 May;28(5):573–582. doi: 10.1136/gut.28.5.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hall P. A., Levison D. A. Review: assessment of cell proliferation in histological material. J Clin Pathol. 1990 Mar;43(3):184–192. doi: 10.1136/jcp.43.3.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hall P. A., Levison D. A., Woods A. L., Yu C. C., Kellock D. B., Watkins J. A., Barnes D. M., Gillett C. E., Camplejohn R., Dover R. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: an index of cell proliferation with evidence of deregulated expression in some neoplasms. J Pathol. 1990 Dec;162(4):285–294. doi: 10.1002/path.1711620403. [DOI] [PubMed] [Google Scholar]
  12. Hall P. A., McKee P. H., Menage H. D., Dover R., Lane D. P. High levels of p53 protein in UV-irradiated normal human skin. Oncogene. 1993 Jan;8(1):203–207. [PubMed] [Google Scholar]
  13. Harrison R. F., Reynolds G. M., Rowlands D. C. Immunohistochemical evidence for the expression of proliferating cell nuclear antigen (PCNA) by non-proliferating hepatocytes adjacent to metastatic tumours and in inflammatory conditions. J Pathol. 1993 Oct;171(2):115–122. doi: 10.1002/path.1711710208. [DOI] [PubMed] [Google Scholar]
  14. Imanishi K., Yamaguchi K., Suzuki M., Honda S., Yanaihara N., Abe K. Production of transforming growth factor-alpha in human tumour cell lines. Br J Cancer. 1989 May;59(5):761–765. doi: 10.1038/bjc.1989.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lemoine N. R., Hughes C. M., Barton C. M., Poulsom R., Jeffery R. E., Klöppel G., Hall P. A., Gullick W. J. The epidermal growth factor receptor in human pancreatic cancer. J Pathol. 1992 Jan;166(1):7–12. doi: 10.1002/path.1711660103. [DOI] [PubMed] [Google Scholar]
  16. McCormick D., Hall P. A. The complexities of proliferating cell nuclear antigen. Histopathology. 1992 Dec;21(6):591–594. doi: 10.1111/j.1365-2559.1992.tb00454.x. [DOI] [PubMed] [Google Scholar]
  17. Ottavio L., Chang C. D., Rizzo M. G., Travali S., Casadevall C., Baserga R. Importance of introns in the growth regulation of mRNA levels of the proliferating cell nuclear antigen gene. Mol Cell Biol. 1990 Jan;10(1):303–309. doi: 10.1128/mcb.10.1.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pelosi G., Zamboni G., Doglioni C., Rodella S., Bresaola E., Iacono C., Serio G., Iannucci A., Scarpa A. Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Am J Surg Pathol. 1992 Dec;16(12):1215–1225. doi: 10.1097/00000478-199212000-00008. [DOI] [PubMed] [Google Scholar]
  19. Sampson S. A., Kreipe H., Gillett C. E., Smith P., Chaudary M. A., Khan A., Wicks K., Parwaresch R., Barnes D. M. KiS1--a novel monoclonal antibody which recognizes proliferating cells: evaluation of its relationship to prognosis in mammary carcinoma. J Pathol. 1992 Oct;168(2):179–185. doi: 10.1002/path.1711680205. [DOI] [PubMed] [Google Scholar]
  20. Scott R. J., Hall P. A., Haldane J. S., van Noorden S., Price Y., Lane D. P., Wright N. A. A comparison of immunohistochemical markers of cell proliferation with experimentally determined growth fraction. J Pathol. 1991 Oct;165(2):173–178. doi: 10.1002/path.1711650213. [DOI] [PubMed] [Google Scholar]
  21. Shipman-Appasamy P., Cohen K. S., Prystowsky M. B. Interleukin 2-induced expression of proliferating cell nuclear antigen is regulated by transcriptional and post-transcriptional mechanisms. J Biol Chem. 1990 Nov 5;265(31):19180–19184. [PubMed] [Google Scholar]
  22. Suzuka I., Daidoji H., Matsuoka M., Kadowaki K., Takasaki Y., Nakane P. K., Moriuchi T. Gene for proliferating-cell nuclear antigen (DNA polymerase delta auxiliary protein) is present in both mammalian and higher plant genomes. Proc Natl Acad Sci U S A. 1989 May;86(9):3189–3193. doi: 10.1073/pnas.86.9.3189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Toschi L., Bravo R. Changes in cyclin/proliferating cell nuclear antigen distribution during DNA repair synthesis. J Cell Biol. 1988 Nov;107(5):1623–1628. doi: 10.1083/jcb.107.5.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Waseem N. H., Lane D. P. Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci. 1990 May;96(Pt 1):121–129. doi: 10.1242/jcs.96.1.121. [DOI] [PubMed] [Google Scholar]

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