, Volume 15, Issue 2, pp 205–211 | Cite as

IGF-I stimulation of extracellular acidification is not linked to cell proliferation for autocrine cells

  • Rose Marie Robinson
  • R. Michael Akers
  • Kimberly E. Forsten


Insulin-like growth factor-I (IGF-I) increases extracellular acidification rate (ECAR), a measure correlated with proliferation for nonautocrine cells. To evaluate the effect of autocrine IGF-I secretion on cell responsiveness, a cell line that secretes IGF-I was tested. SV40-IGF=I cells also registered concentration-dependent increases in ECAR; however, unlike the parental cell line, signal attenuation upon repeat challenges was not evident. Furthermore, SV40-IGF-I cells did not proliferate in response to IGF-I. We investigated if lack of proliferation was due to differences in the protocols, of the assays ([3H]thymidine incorporation and microphysiometry). We identified three key differences in the protocols: surface substrate, cell density, and fluid residence time. We found no increase in [3H]thymidine incorporation for cells on either tissueculture plastic or polycarbonate transwells. Control levels of [3H]thymidine incorporation were cell-density-dependent, but IGF-I did not increase proliferation at any density studied. Finally, we investigated IGF-I stimulation for cells under microphysiometer flow conditions and found no proliferative response to IGF-I. We found that the cells do respond to IGF-I with increased amino acid uptake. These data suggest that IGF-I signaling is operational in the SV40-IGF-I cells, but the transduction pathway for IGF-I-induced proliferation is compromised, despite the fact that these cells respond to fetal bovine serum with increased growth. Ongoing studies are focused on identifying which elements in the signaling cascade are altered by autocrine scretion of IGF-I.

Key Words

Insulin-like growth factor-I (IGF-I) microphysiometer mammary epithelial cells autocrine MAC-T SV40-IGF-I 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Cohick, W. S. (1998). J. Dairy Sci. 81, 1769–1777.PubMedCrossRefGoogle Scholar
  2. 2.
    Kleinberg, D. L. (1997). J. Mam. Gland Biol. Neoplasia 2, 49–57.CrossRefGoogle Scholar
  3. 3.
    Prosser, C. G. (1996). J. Mam. Gland Biol.Neoplasia 1, 297–306.CrossRefGoogle Scholar
  4. 4.
    Akers, R. M., McFadden, T. B., Purup, M., Vestergaard, M., Sejrsen, S., and Capuco, A. V. (2000). J. Mam. Gland Biol. Neoplasia 5, 43–51.CrossRefGoogle Scholar
  5. 5.
    Hovey, R. C., McFadden, T. B., and Akers, R. M. (1998). J. Mam. Gland Biol. Neoplasia 4, 53–68.CrossRefGoogle Scholar
  6. 6.
    Kleinberg, D. L. (1998). Breast Cancer Res. Tr. 47, 201–208.CrossRefGoogle Scholar
  7. 7.
    Forsyth, I. A., Gabai, G., and Morgan, G. (1999). J. Dairy Res. 66, 35–44.PubMedCrossRefGoogle Scholar
  8. 8.
    Marcotty, C., Frankenne, F., Meuris, S., and Hennen, G. (1994). Mol. Cell Endocrinol. 99, 237–243.PubMedCrossRefGoogle Scholar
  9. 9.
    Richert, M. M. and Wood, T. L. (1999). Endocrinology 140, 454–461.PubMedCrossRefGoogle Scholar
  10. 10.
    Hauser, S. D., McGrath, M. F., Collier, R. J., and Krivi, G. G. (1990). Mol. Cell Endocrinol. 72, 187–200.PubMedCrossRefGoogle Scholar
  11. 11.
    Rosen, N., Yee, D., Lippman, M. E., Paik, S., and Cullen, K. J. (1991). Breast Cancer Res. Tr. 18, S35-S62.Google Scholar
  12. 12.
    Weber, M. S., Purup, S., Vestergaard, M., Ellis, S. E., Sondergard-Andersen, J., Akers, R. M., and Sejrsen, K. (1999). J. Endocrinol. 161, 365–373.PubMedCrossRefGoogle Scholar
  13. 13.
    Yee, D., Paik, S., Lebovic, G. S., Marcus, R. R., Favoni, R. E., Cullen, K. J., Lippman, M. E., and Rosen, N. (1989). Mol. Endocrinol. 3, 509–517.PubMedGoogle Scholar
  14. 14.
    Pilichowska, M., Kimura, N., Fujiwara, H., and Nagura, H. (1997). Mod. Pathol. 10, 969–975.PubMedGoogle Scholar
  15. 15.
    Resnicoff, M., Burgaud, J.-L., Rotman, H., Abraham, D., and Baserga, R. (1995). Cancer Res. 55, 3739–3741.PubMedGoogle Scholar
  16. 16.
    Butler, A. A., Blakesley, V. A., Tsokos, M., Plouliki, V., Wood, T., and LeRoith, D. (1998). Cancer Res. 58, 3021–3027.PubMedGoogle Scholar
  17. 17.
    Surmacz, E. (2000). J. Mam. Gland Biol. Neoplasia 5, 95–105.CrossRefGoogle Scholar
  18. 18.
    Sporn. M. B. and Roberts, A. B. (1992). Annals of Int. Med. 117, 408–414.Google Scholar
  19. 19.
    Jones, J. I. and Clemmons, D. R. (1995). Endocrine Rev. 16, 3–34.CrossRefGoogle Scholar
  20. 20.
    Miura, M., Surmacz, E., Burgaud, J.-L., and Baserga, R. (1995). J. Biol. Chem. 270, 22,639–22,644.Google Scholar
  21. 21.
    Sell, C., Rubini, M., Rubin, R., Liu, J.-P., Efstratiadis, A., and Baserga, R. (1993). Proc. Natl. Acad. Sci. USA 90, 11,217–11,221.CrossRefGoogle Scholar
  22. 22.
    Baserga, R. (1999). Exp. Cell Res. 253, 1–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Hongo, A., D'Ambrosio, C., Miura, M., Morrione, A., and Baserga, R. (1996). Oncogene 12, 1231–1238.PubMedGoogle Scholar
  24. 24.
    Quinn, K. A., Treston, A. M., Unsworth, E. J., Miller, M., Vos, M., Grimley, C., Battey, J., Mulshine, J. L., and Cuttitta, F. (1996). J. Biol. Chem. 271, 11,477–11,483.Google Scholar
  25. 25.
    Osborne, C. K., Coronado, E. B., Kitten, L. J., Arteaga, C. I. Fuqua, S. A. W., Ramasharma, K., Marshall, M., and Li, C. H. (1989). Mol. Endocrinol. 3, 1701–1709.PubMedGoogle Scholar
  26. 26.
    Lee, A. V., Darbre, P., and King. R. J. B. (1994). Mol. Cell Endocrinol. 99, 211–220.PubMedCrossRefGoogle Scholar
  27. 27.
    Robinson, R. M., Akers, R. M., and Forsten, K. E. (2000). Endocrine 13, 345–352.PubMedCrossRefGoogle Scholar
  28. 28.
    McConnell, H. M., Owicki, J. C., parce, J. W., Miller, D. L., Baxter, G. T., Wada, H. G., and Pitchford, S. (1992). Science 257, 1906–1912.PubMedCrossRefGoogle Scholar
  29. 29.
    Romagnolo, D., Akers, R. M., Byatt, J. C., Wong, E. A., and Turner, J. D. (1994). Endocrine J. 2, 375–384.Google Scholar
  30. 30.
    Conover, C. A., Bale, L. K., Durham, S. K., and Powell, D. R. (2000). Endocrinology 141, 3098–3103.PubMedCrossRefGoogle Scholar
  31. 31.
    Osborn, C. K., Clemmons, D. R., and Arteaga, C. L. (1990). Biochem. Molec. Biol. 37, 805–809.Google Scholar
  32. 32.
    Lauffenburger, D. A., Oehrtman, G. T., Walker, L., and Wiley, H. S. (1998). Proc. Natl. Acad. Sci. USA 95, 15,368–15,373.CrossRefGoogle Scholar
  33. 33.
    Laping, N. J., Olson, B. A., DeWolf, R. E., Albrightson, C. R., Fredickson, T., King, C., Chirivella, M., Ziyadeh, F. N., and Nambi, P. (1998). Biochem. Pharmacol. 55, 227–234.PubMedCrossRefGoogle Scholar
  34. 34.
    Chan, S. D. H., Antoniucci, D. M., Fok, K.S., Alajoki, M. L., Harkins, R. N., Thompson, S. A., and Wada, H. G. (1995). J. Biol. Chem. 270, 22,608–22,613.CrossRefGoogle Scholar
  35. 35.
    Oehrtman, G., Walker, L., Will, B., Opresko, L., Wiley, H. S., and Lauffenburger, D. A. (1999). Quantitative Assessment of Autocrine Cell Loops, in Tissue Energeering Methods and Protocols. Morgan, J. R. and Yarmush, M. L. (eds.). Humana Press, Inc., Totowa, NJ. pp. 143–154.Google Scholar
  36. 36.
    Cascieri, M. A., Hayes, N. S., Kelder, B., Kopchick, J. J., Chicchi, G. G., Slater, E. E., and Bayne, M. L. (1988). Endocrinology 122, 1314–1320.PubMedCrossRefGoogle Scholar
  37. 37.
    Wang, L. and Adamo, M. L. (2000). Endocrinology 141, 2481–2489.PubMedCrossRefGoogle Scholar
  38. 38.
    Capone, A., Visco, V., Belleudi, F., Marchese, C., Cardinali, G., Bellocci, M., Picardo, M., Frati, L., and Torrisi, M. R. (2000). Cell Growth. Differ. 11, 607–614.PubMedGoogle Scholar
  39. 39.
    Politis, I., Zavizion, B., White, J. H., Goldberg, J. J., Baldi, A., and Akers, R. M. (1995). Endocrine 3, 345–350.CrossRefGoogle Scholar
  40. 40.
    Woodward, T. L., Lu, H., and Haslam, S. Z. (2000). Endocrinology 141, 2814–2821.PubMedCrossRefGoogle Scholar
  41. 41.
    Villars, F., Conrad, V., Rouais, F., Lefebvre, F., Amedee, J., and Bordenave, L. (1996). Cell Biol. Toxicol. 12, 207–214.PubMedCrossRefGoogle Scholar
  42. 42.
    Forsten, K. E. and Lauffenburger, D. A. (1994). J. Comput. Biol. 1, 15–23.PubMedGoogle Scholar
  43. 43.
    Santhanagopal, A. and Dixon, S. J. (1999). Am. J. Physiol. 277, E423-E432.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2001

Authors and Affiliations

  • Rose Marie Robinson
    • 1
  • R. Michael Akers
    • 2
  • Kimberly E. Forsten
    • 1
  1. 1.Department of Chemical EngineeringVirginia Polytechnic Institute and State UniversityBlacksburg
  2. 2.Department of Dairy ScienceVirginia Polytechnic Institute and State UniversityBlacksburg

Personalised recommendations