Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jan;69(1):130–134. doi: 10.1038/bjc.1994.21

Induction of transforming growth factor beta in hormonally treated human prostate cancer.

G H Muir 1, A Butta 1, R J Shearer 1, C Fisher 1, D P Dearnaley 1, K C Flanders 1, M B Sporn 1, A A Colletta 1
PMCID: PMC1968789  PMID: 8286194

Abstract

Transforming growth factor beta-1 (TGF-beta 1) has been proposed as a mediator of tumour growth in a number of tumours and cell lines including prostate, and in a recent study was shown to be up-regulated in the stroma of breast cancer tissue following treatment with the anti-oestrogen tamoxifen. Immunolocalisation of the intracellular form of TGF-beta 1 confirmed that the source of the stromal TGF-beta 1 was the peritumoral fibroblasts. We present here the results of a study in which five patients with hormonally unresponsive prostatic carcinoma and seven patients responding to a luteinising hormone-releasing hormone analogue had prostate biopsies taken before and during treatment. These were stained for TGF-beta expression prior to treatment and at either relapse or 3 months later respectively. Six of seven clinically responding tumours and three of five relapsed tumours showed up-regulation of extracellular TGF-beta 1, again primarily in the stroma, with no apparent up-regulation of intracellular TGF-beta 1, TGF-beta 2 or TGF-beta 3. These data illustrate that the epithelial growth inhibitor TGF-beta 1 can be induced by hormonal manipulation in prostate cancer in vivo, and may continue to be up-regulated even after relapse. This suggests that relapse of hormonally treated prostate cancer may be associated with a failure of the epithelium to respond to stromal TGF-beta 1.

Full text

PDF
130

Images in this article

Selected References

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

  1. Butta A., MacLennan K., Flanders K. C., Sacks N. P., Smith I., McKinna A., Dowsett M., Wakefield L. M., Sporn M. B., Baum M. Induction of transforming growth factor beta 1 in human breast cancer in vivo following tamoxifen treatment. Cancer Res. 1992 Aug 1;52(15):4261–4264. [PubMed] [Google Scholar]
  2. Colletta A. A., Kealey T. cDNA cloning of a human androgen-induced mRNA exhibiting an early and protein synthesis-independent induction. FEBS Lett. 1991 Oct 7;291(1):132–134. doi: 10.1016/0014-5793(91)81120-w. [DOI] [PubMed] [Google Scholar]
  3. Colletta A. A., Wakefield L. M., Howell F. V., Danielpour D., Baum M., Sporn M. B. The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta. J Clin Invest. 1991 Jan;87(1):277–283. doi: 10.1172/JCI114983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cunha G. R., Donjacour A. Stromal-epithelial interactions in normal and abnormal prostatic development. Prog Clin Biol Res. 1987;239:251–272. [PubMed] [Google Scholar]
  5. Flanders K. C., Thompson N. L., Cissel D. S., Van Obberghen-Schilling E., Baker C. C., Kass M. E., Ellingsworth L. R., Roberts A. B., Sporn M. B. Transforming growth factor-beta 1: histochemical localization with antibodies to different epitopes. J Cell Biol. 1989 Feb;108(2):653–660. doi: 10.1083/jcb.108.2.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fosså S. D., Dearnaley D. P., Law M., Gad J., Newling D. W., Tveter K. Prognostic factors in hormone-resistant progressing cancer of the prostate. Ann Oncol. 1992 May;3(5):361–366. doi: 10.1093/oxfordjournals.annonc.a058207. [DOI] [PubMed] [Google Scholar]
  7. Glick A. B., McCune B. K., Abdulkarem N., Flanders K. C., Lumadue J. A., Smith J. M., Sporn M. B. Complex regulation of TGF beta expression by retinoic acid in the vitamin A-deficient rat. Development. 1991 Apr;111(4):1081–1086. doi: 10.1242/dev.111.4.1081. [DOI] [PubMed] [Google Scholar]
  8. Goldstein D., O'Leary M., Mitchen J., Borden E. C., Wilding G. Effects of interferon beta ser and transforming growth factor beta on prostatic cell lines. J Urol. 1991 Oct;146(4):1173–1177. doi: 10.1016/s0022-5347(17)38034-5. [DOI] [PubMed] [Google Scholar]
  9. Henriksson P., Edhag O. Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects. Br Med J (Clin Res Ed) 1986 Aug 16;293(6544):413–415. doi: 10.1136/bmj.293.6544.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kim S. J., Park K., Koeller D., Kim K. Y., Wakefield L. M., Sporn M. B., Roberts A. B. Post-transcriptional regulation of the human transforming growth factor-beta 1 gene. J Biol Chem. 1992 Jul 5;267(19):13702–13707. [PubMed] [Google Scholar]
  11. Knabbe C., Lippman M. E., Wakefield L. M., Flanders K. C., Kasid A., Derynck R., Dickson R. B. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987 Feb 13;48(3):417–428. doi: 10.1016/0092-8674(87)90193-0. [DOI] [PubMed] [Google Scholar]
  12. Kooistra A., König J. J., Romijn J. C., Schröder F. H. Negative control of epithelial cell proliferation by prostatic stroma. Anticancer Res. 1991 Jul-Aug;11(4):1495–1500. [PubMed] [Google Scholar]
  13. Kyprianou N., Isaacs J. T. Expression of transforming growth factor-beta in the rat ventral prostate during castration-induced programmed cell death. Mol Endocrinol. 1989 Oct;3(10):1515–1522. doi: 10.1210/mend-3-10-1515. [DOI] [PubMed] [Google Scholar]
  14. Kyprianou N., Isaacs J. T. Identification of a cellular receptor for transforming growth factor-beta in rat ventral prostate and its negative regulation by androgens. Endocrinology. 1988 Oct;123(4):2124–2131. doi: 10.1210/endo-123-4-2124. [DOI] [PubMed] [Google Scholar]
  15. Limonta P., Dondi D., Moretti R. M., Maggi R., Motta M. Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP. J Clin Endocrinol Metab. 1992 Jul;75(1):207–212. doi: 10.1210/jcem.75.1.1320049. [DOI] [PubMed] [Google Scholar]
  16. Martikainen P., Kyprianou N., Isaacs J. T. Effect of transforming growth factor-beta 1 on proliferation and death of rat prostatic cells. Endocrinology. 1990 Dec;127(6):2963–2968. doi: 10.1210/endo-127-6-2963. [DOI] [PubMed] [Google Scholar]
  17. Merz V. W., Miller G. J., Krebs T., Timme T. L., Kadmon D., Park S. H., Egawa S., Scardino P. T., Thompson T. C. Elevated transforming growth factor-beta 1 and beta 3 mRNA levels are associated with ras + myc-induced carcinomas in reconstituted mouse prostate: evidence for a paracrine role during progression. Mol Endocrinol. 1991 Apr;5(4):503–513. doi: 10.1210/mend-5-4-503. [DOI] [PubMed] [Google Scholar]
  18. Qayum A., Gullick W., Clayton R. C., Sikora K., Waxman J. The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors. Br J Cancer. 1990 Jul;62(1):96–99. doi: 10.1038/bjc.1990.236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schulz P., Bauer H. W., Brade W. P., Keller A., Fittler F. Evaluation of the cytotoxic activity of diethylstilbestrol and its mono- and diphosphate towards prostatic carcinoma cells. Cancer Res. 1988 May 15;48(10):2867–2870. [PubMed] [Google Scholar]
  20. Schuurmans A. L., Bolt J., Veldscholte J., Mulder E. Regulation of growth of LNCaP human prostate tumor cells by growth factors and steroid hormones. J Steroid Biochem Mol Biol. 1991;40(1-3):193–197. doi: 10.1016/0960-0760(91)90182-5. [DOI] [PubMed] [Google Scholar]
  21. Shearer R. J., Davies J. H., Gelister J. S., Dearnaley D. P. Hormonal cytoreduction and radiotherapy for carcinoma of the prostate. Br J Urol. 1992 May;69(5):521–524. doi: 10.1111/j.1464-410x.1992.tb15601.x. [DOI] [PubMed] [Google Scholar]
  22. Steiner M. S., Barrack E. R. Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. Mol Endocrinol. 1992 Jan;6(1):15–25. doi: 10.1210/mend.6.1.1738367. [DOI] [PubMed] [Google Scholar]
  23. Wakefield L. M., Sporn M. B. Suppression of carcinogenesis: a role for TGF-beta and related molecules in prevention of cancer. Immunol Ser. 1990;51:217–243. [PubMed] [Google Scholar]
  24. Whitmore W. F., Jr Natural history and staging of prostate cancer. Urol Clin North Am. 1984 May;11(2):205–220. [PubMed] [Google Scholar]

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

RESOURCES