Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Oct;62(4):579–584. doi: 10.1038/bjc.1990.333

Production and response of a human prostatic cancer line to transforming growth factor-like molecules.

A MacDonald 1, G D Chisholm 1, F K Habib 1
PMCID: PMC1971489  PMID: 2223575

Abstract

Serum-free media conditioned by the androgen insensitive human prostate cancer cell line DU145 showed immunological transforming growth factor-alpha (TGF alpha) activity, as well as competing activity in epidermal growth factor (EGF) radioreceptor assays (RRA). Furthermore, there were factors in the conditioned media which inhibited and stimulated DNA synthesis by DU145 cells in a dose-dependent fashion. Fractionation of the concentrated conditioned media by reverse-phase high performance liquid chromatography revealed several peaks containing EGF-like competitive activity only one of which demonstrated TGF alpha activity. However, none of the peaks corresponded to immunoreactive EGF. Measurement of EGF receptors on DU145 cells by competition and saturation analysis revealed high levels of receptors (mean +/- s.d. = 2.5 +/- 1 x 10(5) surface receptors per cell) which were of high affinity (Kd +/- s.d. = 1.0 +/- 0.5 nmol l-1). Although DU145 cells express high levels of EGF receptors, DNA synthesis was only minimally affected by exogenous EGF and TGF alpha.

Full text

PDF
579

Selected References

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

  1. Bascom C. C., Sipes N. J., Coffey R. J., Moses H. L. Regulation of epithelial cell proliferation by transforming growth factors. J Cell Biochem. 1989 Jan;39(1):25–32. doi: 10.1002/jcb.240390104. [DOI] [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: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. Brown K. D., Blakeley D. M. Transforming growth factors: sources, properties and possible roles in normal and malignant cell growth control. Biochem Soc Trans. 1984 Apr;12(2):168–173. doi: 10.1042/bst0120168. [DOI] [PubMed] [Google Scholar]
  4. Cherington P. V., Smith B. L., Pardee A. B. Loss of epidermal growth factor requirement and malignant transformation. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3937–3941. doi: 10.1073/pnas.76.8.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Coffey R. J., Jr, Shipley G. D., Moses H. L. Production of transforming growth factors by human colon cancer lines. Cancer Res. 1986 Mar;46(3):1164–1169. [PubMed] [Google Scholar]
  6. Connolly J. M., Rose D. P. Secretion of epidermal growth factor and related polypeptides by the DU 145 human prostate cancer cell line. Prostate. 1989;15(2):177–186. doi: 10.1002/pros.2990150211. [DOI] [PubMed] [Google Scholar]
  7. DeLean A., Munson P. J., Rodbard D. Simultaneous analysis of families of sigmoidal curves: application to bioassay, radioligand assay, and physiological dose-response curves. Am J Physiol. 1978 Aug;235(2):E97–102. doi: 10.1152/ajpendo.1978.235.2.E97. [DOI] [PubMed] [Google Scholar]
  8. Dickson R. B., Bates S. E., McManaway M. E., Lippman M. E. Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res. 1986 Apr;46(4 Pt 1):1707–1713. [PubMed] [Google Scholar]
  9. Ibbotson K. J., Harrod J., Gowen M., D'Souza S., Smith D. D., Winkler M. E., Derynck R., Mundy G. R. Human recombinant transforming growth factor alpha stimulates bone resorption and inhibits formation in vitro. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2228–2232. doi: 10.1073/pnas.83.7.2228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Marquardt H., Hunkapiller M. W., Hood L. E., Twardzik D. R., De Larco J. E., Stephenson J. R., Todaro G. J. Transforming growth factors produced by retrovirus-transformed rodent fibroblasts and human melanoma cells: amino acid sequence homology with epidermal growth factor. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4684–4688. doi: 10.1073/pnas.80.15.4684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Massagué J. Epidermal growth factor-like transforming growth factor. II. Interaction with epidermal growth factor receptors in human placenta membranes and A431 cells. J Biol Chem. 1983 Nov 25;258(22):13614–13620. [PubMed] [Google Scholar]
  12. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  13. Perroteau I., Salomon D., DeBortoli M., Kidwell W., Hazarika P., Pardue R., Dedman J., Tam J. Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat. 1986;7(3):201–210. doi: 10.1007/BF01806251. [DOI] [PubMed] [Google Scholar]
  14. Salomon D. S., Perroteau I., Kidwell W. R., Tam J., Derynck R. Loss of growth responsiveness to epidermal growth factor and enhanced production of alpha-transforming growth factors in ras-transformed mouse mammary epithelial cells. J Cell Physiol. 1987 Mar;130(3):397–409. doi: 10.1002/jcp.1041300313. [DOI] [PubMed] [Google Scholar]
  15. Sporn M. B., Roberts A. B. Autocrine growth factors and cancer. 1985 Feb 28-Mar 6Nature. 313(6005):745–747. doi: 10.1038/313745a0. [DOI] [PubMed] [Google Scholar]
  16. Sporn M. B., Todaro G. J. Autocrine secretion and malignant transformation of cells. N Engl J Med. 1980 Oct 9;303(15):878–880. doi: 10.1056/NEJM198010093031511. [DOI] [PubMed] [Google Scholar]
  17. Stern P. H., Krieger N. S., Nissenson R. A., Williams R. D., Winkler M. E., Derynck R., Strewler G. J. Human transforming growth factor-alpha stimulates bone resorption in vitro. J Clin Invest. 1985 Nov;76(5):2016–2019. doi: 10.1172/JCI112202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Stone K. R., Mickey D. D., Wunderli H., Mickey G. H., Paulson D. F. Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer. 1978 Mar 15;21(3):274–281. doi: 10.1002/ijc.2910210305. [DOI] [PubMed] [Google Scholar]
  19. Stromberg K., Hudgins W. R., Fryling C. M., Hazarika P., Dedman J. R., Pardue R. L., Hargreaves W. R., Orth D. N. Human A673 cells secrete high molecular weight EGF-receptor binding growth factors that appear to be immunologically unrelated to EGF or TGF-alpha. J Cell Biochem. 1986;32(4):247–259. doi: 10.1002/jcb.240320402. [DOI] [PubMed] [Google Scholar]
  20. Valverius E. M., Bates S. E., Stampfer M. R., Clark R., McCormick F., Salomon D. S., Lippman M. E., Dickson R. B. Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells. Mol Endocrinol. 1989 Jan;3(1):203–214. doi: 10.1210/mend-3-1-203. [DOI] [PubMed] [Google Scholar]
  21. Verbeek W., Bokemeyer C., Falk H., Schmoll H. J. Growth requirements, growth factor responsiveness, and growth factor secretion of three human embryonal carcinoma cell lines. J Cancer Res Clin Oncol. 1988;114(6):553–558. doi: 10.1007/BF00398176. [DOI] [PubMed] [Google Scholar]
  22. Wilding G., Valverius E., Knabbe C., Gelmann E. P. Role of transforming growth factor-alpha in human prostate cancer cell growth. Prostate. 1989;15(1):1–12. doi: 10.1002/pros.2990150102. [DOI] [PubMed] [Google Scholar]
  23. Wollenberg G. K., Harris L., Farber E., Hayes M. A. Inverse relationship between epidermal growth factor induced proliferation and expression of high affinity surface epidermal growth factor receptors in rat hepatocytes. Lab Invest. 1989 Feb;60(2):254–259. [PubMed] [Google Scholar]
  24. Zwiebel J. A., Davis M. R., Kohn E., Salomon D. S., Kidwell W. R. Anchorage-independent growth-conferring factor production by rat mammary tumor cells. Cancer Res. 1982 Dec;42(12):5117–5125. [PubMed] [Google Scholar]
  25. van Zoelen E. J., van Rooijen M. A., van Oostwaard T. M., de Laat S. W. Production of transforming growth factors by simian sarcoma virus-transformed cells. Cancer Res. 1987 Mar 15;47(6):1582–1587. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES