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. 1996 Jun;73(11):1356–1361. doi: 10.1038/bjc.1996.258

Defective interleukin six expression and responsiveness in human mammary cells transformed by an adeno 5/SV40 hybrid virus.

F Basolo 1, L Fiore 1, S Calvo 1, V Falcone 1, P G Conaldi 1, G Fontanini 1, A M Caligo 1, G Merlo 1, Y Gluzman 1, A Toniolo 1
PMCID: PMC2074491  PMID: 8645579

Abstract

Mammary epithelial cells (MECs) were isolated and cultured from mammary glands of healthy women undergoing reduction mammoplasty. Normal MECs were infected with the transforming hybrid virus adeno-5/SV40. Two transformed epithelial cell lines, M1 and M2, were obtained, characterised phenotypically and studied for the production of and the response to cytokines and growth regulators. In both cell lines, expression of the SV40 large T antigen was associated with loss of interleukin 6 (IL-6) production and responsiveness as well as with down-regulation of IL-8 and transforming growth factor (TGF)-alpha production. Both M1 and M2 cell lines were capable of forming colonies in semisolid media, but upon injection into severe combined immunodeficient (SCID) mice only M2 cells were tumorigenic. DNA synthesis in M1 cells was partially inhibited by serum or TNF-alpha and weakly stimulated by hydrocortisone (HC) and IL-8. In contrast, M2 cells were totally unresponsive to a variety of growth regulators. Both lines overexpressed the p53 protein at levels about 20-fold higher than those observed in primary MEC cultures, but no mutations of the p53 gene could be detected. The date confirm the view that the expression in human mammary cells of different oncogenes - including the SV40 T antigen - is frequently associated with alterations of cytokine production and responsiveness.

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Selected References

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

  1. Albini A., Aukerman S. L., Ogle R. C., Noonan D. M., Fridman R., Martin G. R., Fidler I. J. The in vitro invasiveness and interactions with laminin of K-1735 melanoma cells. Evidence for different laminin-binding affinities in high and low metastatic variants. Clin Exp Metastasis. 1989 Jul-Aug;7(4):437–451. doi: 10.1007/BF01753664. [DOI] [PubMed] [Google Scholar]
  2. Bartek J., Bartkova J., Kyprianou N., Lalani E. N., Staskova Z., Shearer M., Chang S., Taylor-Papadimitriou J. Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3520–3524. doi: 10.1073/pnas.88.9.3520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Basolo F., Calvo S., Fiore L., Conaldi P. G., Falcone V., Toniolo A. Growth-stimulating activity of interleukin 6 on human mammary epithelial cells transfected with the int-2 gene. Cancer Res. 1993 Jul 1;53(13):2957–2960. [PubMed] [Google Scholar]
  4. Basolo F., Fiore L., Ciardiello F., Calvo S., Fontanini G., Conaldi P. G., Toniolo A. Response of normal and oncogene-transformed human mammary epithelial cells to transforming growth factor beta 1 (TGF-beta 1): lack of growth-inhibitory effect on cells expressing the simian virus 40 large-T antigen. Int J Cancer. 1994 Mar 1;56(5):736–742. doi: 10.1002/ijc.2910560521. [DOI] [PubMed] [Google Scholar]
  5. Basolo F., Serra C., Ciardiello F., Fiore L., Russo J., Campani D., Dolei A., Squartini F., Toniolo A. Regulation of surface-differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene. Int J Cancer. 1992 Jun 19;51(4):634–640. doi: 10.1002/ijc.2910510421. [DOI] [PubMed] [Google Scholar]
  6. Berthon P., Goubin G., Dutrillaux B., Degeorges A., Faille A., Gespach C., Calvo F. Single-steep transformation of human breast epithelial cells by SV40 large T oncogene. Int J Cancer. 1992 Aug 19;52(1):92–97. doi: 10.1002/ijc.2910520117. [DOI] [PubMed] [Google Scholar]
  7. Bártek J., Vojtesek B., Lane D. P. Diversity of human p53 mutants revealed by complex formation to SV40 T antigen. Eur J Cancer. 1992;29A(1):101–107. doi: 10.1016/0959-8049(93)90584-3. [DOI] [PubMed] [Google Scholar]
  8. Calaf G., Russo J. Transformation of human breast epithelial cells by chemical carcinogens. Carcinogenesis. 1993 Mar;14(3):483–492. doi: 10.1093/carcin/14.3.483. [DOI] [PubMed] [Google Scholar]
  9. Chang F., Syrjänen S., Tervahauta A., Syrjänen K. Tumourigenesis associated with the p53 tumour suppressor gene. Br J Cancer. 1993 Oct;68(4):653–661. doi: 10.1038/bjc.1993.404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ciardiello F., Gottardis M., Basolo F., Pepe S., Normanno N., Dickson R. B., Bianco A. R., Salomon D. S. Additive effects of c-erbB-2, c-Ha-ras, and transforming growth factor-alpha genes on in vitro transformation of human mammary epithelial cells. Mol Carcinog. 1992;6(1):43–52. doi: 10.1002/mc.2940060108. [DOI] [PubMed] [Google Scholar]
  11. Delmolino L., Band H., Band V. Expression and stability of p53 protein in normal human mammary epithelial cells. Carcinogenesis. 1993 May;14(5):827–832. doi: 10.1093/carcin/14.5.827. [DOI] [PubMed] [Google Scholar]
  12. Emerman J. T., Eaves C. J. Lack of effect of hematopoietic growth factors on human breast epithelial cell growth in serum-free primary culture. Bone Marrow Transplant. 1994 Mar;13(3):285–291. [PubMed] [Google Scholar]
  13. Eriksson E. T., Schimmelpenning H., Aspenblad U., Zetterberg A., Auer G. U. Immunohistochemical expression of the mutant p53 protein and nuclear DNA content during the transition from benign to malignant breast disease. Hum Pathol. 1994 Nov;25(11):1228–1233. doi: 10.1016/0046-8177(94)90040-x. [DOI] [PubMed] [Google Scholar]
  14. Herman M. E., Katzenellenbogen B. S. Alterations in transforming growth factor-alpha and -beta production and cell responsiveness during the progression of MCF-7 human breast cancer cells to estrogen-autonomous growth. Cancer Res. 1994 Nov 15;54(22):5867–5874. [PubMed] [Google Scholar]
  15. Lehman T. A., Modali R., Boukamp P., Stanek J., Bennett W. P., Welsh J. A., Metcalf R. A., Stampfer M. R., Fusenig N., Rogan E. M. p53 mutations in human immortalized epithelial cell lines. Carcinogenesis. 1993 May;14(5):833–839. doi: 10.1093/carcin/14.5.833. [DOI] [PubMed] [Google Scholar]
  16. Ludlow J. W. Interactions between SV40 large-tumor antigen and the growth suppressor proteins pRB and p53. FASEB J. 1993 Jul;7(10):866–871. doi: 10.1096/fasebj.7.10.8344486. [DOI] [PubMed] [Google Scholar]
  17. Ochieng J., Basolo F., Albini A., Melchiori A., Watanabe H., Elliott J., Raz A., Parodi S., Russo J. Increased invasive, chemotactic and locomotive abilities of c-Ha-ras-transformed human breast epithelial cells. Invasion Metastasis. 1991;11(1):38–47. [PubMed] [Google Scholar]
  18. Paine T. M., Soule H. D., Pauley R. J., Dawson P. J. Characterization of epithelial phenotypes in mortal and immortal human breast cells. Int J Cancer. 1992 Feb 1;50(3):463–473. doi: 10.1002/ijc.2910500323. [DOI] [PubMed] [Google Scholar]
  19. Petersen O. W., Rønnov-Jessen L., Howlett A. R., Bissell M. J. Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064–9068. doi: 10.1073/pnas.89.19.9064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Raux H., Planchon P., Chraibi-Hajji F., Magnien V., Sallé V., Brouty-Boyé D. Immunophenotype of SV40-T gene transfected epithelial cell lines derived from human benign breast tumors. In Vitro Cell Dev Biol. 1992 Jul-Aug;28A(7-8):468–470. doi: 10.1007/BF02634127. [DOI] [PubMed] [Google Scholar]
  21. Reiss M., Vellucci V. F., Zhou Z. L. Mutant p53 tumor suppressor gene causes resistance to transforming growth factor beta 1 in murine keratinocytes. Cancer Res. 1993 Feb 15;53(4):899–904. [PubMed] [Google Scholar]
  22. Shearer M., Bartkova J., Bartek J., Berdichevsky F., Barnes D., Millis R., Taylor-Papadimitriou J. Studies of clonal cell lines developed from primary breast cancers indicate that the ability to undergo morphogenesis in vitro is lost early in malignancy. Int J Cancer. 1992 Jun 19;51(4):602–612. doi: 10.1002/ijc.2910510417. [DOI] [PubMed] [Google Scholar]
  23. Soule H. D., Maloney T. M., Wolman S. R., Peterson W. D., Jr, Brenz R., McGrath C. M., Russo J., Pauley R. J., Jones R. F., Brooks S. C. Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10. Cancer Res. 1990 Sep 15;50(18):6075–6086. [PubMed] [Google Scholar]
  24. Taylor-Papadimitriou J., Stampfer M., Bartek J., Lewis A., Boshell M., Lane E. B., Leigh I. M. Keratin expression in human mammary epithelial cells cultured from normal and malignant tissue: relation to in vivo phenotypes and influence of medium. J Cell Sci. 1989 Nov;94(Pt 3):403–413. doi: 10.1242/jcs.94.3.403. [DOI] [PubMed] [Google Scholar]
  25. Van Doren K., Gluzman Y. Efficient transformation of human fibroblasts by adenovirus-simian virus 40 recombinants. Mol Cell Biol. 1984 Aug;4(8):1653–1656. doi: 10.1128/mcb.4.8.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Yilmaz A., Gaide A. C., Sordat B., Borbenyi Z., Lahm H., Imam A., Schreyer M., Odartchenko N. Malignant progression of SV40-immortalised human milk epithelial cells. Br J Cancer. 1993 Nov;68(5):868–873. doi: 10.1038/bjc.1993.447. [DOI] [PMC free article] [PubMed] [Google Scholar]

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