Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jun;69(6):1006–1009. doi: 10.1038/bjc.1994.197

Expression of transforming growth factor beta mRNA isoforms in human breast cancer.

J MacCallum 1, J M Bartlett 1, A M Thompson 1, J C Keen 1, J M Dixon 1, W R Miller 1
PMCID: PMC1969445  PMID: 8198961

Abstract

Using an RNAse protection assay, expression of messenger RNA for isoforms of TGF-beta was determined in a series of breast cancers. Of 50 tumours, 45 (90%) expressed TGF-beta 1 mRNA, 39 (78%) expressed TGF-beta 2, and 47 (94%) expressed TGF-beta 3. Patterns of expression varied between different tumours: 37 (74%) cancers expressed all three TGF-beta isoforms, ten (20%) expressed only two isoforms and two expressed TGF-beta 1 alone. One sample showed no evidence of TGF-beta mRNA expression. Although most breast cancers expressed mRNA for at least one isoform of TGF-beta, there were differences in patterns of mRNA expression between individual tumours. The relatively small number of tumours examined precluded detailed analysis between expression and other clinical parameters, but a significant association was identified between one aspect of isoform expression and lymph node status, in that the majority of tumours expressing all three isoforms were associated with lymph node involvement, whereas tumours without one or more isoform were usually lymph node negative (P = 0.025 by Fisher's exact test).

Full text

PDF
1006

Images in this article

Selected References

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

  1. Anderson E. D., Forrest A. P., Levack P. A., Chetty U., Hawkins R. A. Response to endocrine manipulation and oestrogen receptor concentration in large operable primary breast cancer. Br J Cancer. 1989 Aug;60(2):223–226. doi: 10.1038/bjc.1989.256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arrick B. A., Korc M., Derynck R. Differential regulation of expression of three transforming growth factor beta species in human breast cancer cell lines by estradiol. Cancer Res. 1990 Jan 15;50(2):299–303. [PubMed] [Google Scholar]
  3. Arteaga C. L., Coffey R. J. Transforming growth factor-beta isoforms in mammary neoplasia: more questions than answers. Hum Pathol. 1992 Jan;23(1):1–3. doi: 10.1016/0046-8177(92)90002-k. [DOI] [PubMed] [Google Scholar]
  4. Assoian R. K., Fleurdelys B. E., Stevenson H. C., Miller P. J., Madtes D. K., Raines E. W., Ross R., Sporn M. B. Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6020–6024. doi: 10.1073/pnas.84.17.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  6. Barrett-Lee P., Travers M., Luqmani Y., Coombes R. C. Transcripts for transforming growth factors in human breast cancer: clinical correlates. Br J Cancer. 1990 Apr;61(4):612–617. doi: 10.1038/bjc.1990.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bartlett J. M., Rabiasz G. J., Scott W. N., Langdon S. P., Smyth J. F., Miller W. R. Transforming growth factor-beta mRNA expression and growth control of human ovarian carcinoma cells. Br J Cancer. 1992 May;65(5):655–660. doi: 10.1038/bjc.1992.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Dalal B. I., Keown P. A., Greenberg A. H. Immunocytochemical localization of secreted transforming growth factor-beta 1 to the advancing edges of primary tumors and to lymph node metastases of human mammary carcinoma. Am J Pathol. 1993 Aug;143(2):381–389. [PMC free article] [PubMed] [Google Scholar]
  10. Delvenne C. G., Winkler-Gol R. A., Piccart M. J., Hustin J., Michaux D., Leclercq G., Nogaret J. M., Autier P. Expression of c-erbB2, TGF-beta 1 and pS2 genes in primary human breast cancers. Eur J Cancer. 1992;28(2-3):700–705. doi: 10.1016/s0959-8049(05)80130-3. [DOI] [PubMed] [Google Scholar]
  11. Gorsch S. M., Memoli V. A., Stukel T. A., Gold L. I., Arrick B. A. Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res. 1992 Dec 15;52(24):6949–6952. [PubMed] [Google Scholar]
  12. Hawkins R. A., Hill A., Freedman B. A simple method for the determination of oestrogen receptor concentrations in breast tumours and other tissues. Clin Chim Acta. 1975 Oct 15;64(2):203–210. doi: 10.1016/0009-8981(75)90202-8. [DOI] [PubMed] [Google Scholar]
  13. Hsuan J. J. Transforming growth factors beta. Br Med Bull. 1989 Apr;45(2):425–437. doi: 10.1093/oxfordjournals.bmb.a072332. [DOI] [PubMed] [Google Scholar]
  14. Ikeda T., Lioubin M. N., Marquardt H. Human transforming growth factor type beta 2: production by a prostatic adenocarcinoma cell line, purification, and initial characterization. Biochemistry. 1987 May 5;26(9):2406–2410. doi: 10.1021/bi00383a002. [DOI] [PubMed] [Google Scholar]
  15. Jeng M. H., Jordan V. C. Growth stimulation and differential regulation of transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, and TGF beta 3 messenger RNA levels by norethindrone in MCF-7 human breast cancer cells. Mol Endocrinol. 1991 Aug;5(8):1120–1128. doi: 10.1210/mend-5-8-1120. [DOI] [PubMed] [Google Scholar]
  16. Kehrl J. H., Wakefield L. M., Roberts A. B., Jakowlew S., Alvarez-Mon M., Derynck R., Sporn M. B., Fauci A. S. Production of transforming growth factor beta by human T lymphocytes and its potential role in the regulation of T cell growth. J Exp Med. 1986 May 1;163(5):1037–1050. doi: 10.1084/jem.163.5.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Knabbe C., Zugmaier G., Schmahl M., Dietel M., Lippman M. E., Dickson R. B. Induction of transforming growth factor beta by the antiestrogens droloxifene, tamoxifen, and toremifene in MCF-7 cells. Am J Clin Oncol. 1991;14 (Suppl 2):S15–S20. doi: 10.1097/00000421-199112002-00005. [DOI] [PubMed] [Google Scholar]
  19. Lippman M. E., Dickson R. B., Gelmann E. P., Rosen N., Knabbe C., Bates S., Bronzert D., Huff K., Kasid A. Growth regulation of human breast carcinoma occurs through regulated growth factor secretion. J Cell Biochem. 1987 Sep;35(1):1–16. doi: 10.1002/jcb.240350102. [DOI] [PubMed] [Google Scholar]
  20. Maier R., Schmid P., Cox D., Bilbe G., McMaster G. K. Localization of transforming growth factor-beta 1, -beta 2 and -beta 3 gene expression in bovine mammary gland. Mol Cell Endocrinol. 1991 Dec;82(2-3):191–198. doi: 10.1016/0303-7207(91)90031-m. [DOI] [PubMed] [Google Scholar]
  21. Massagué J. The TGF-beta family of growth and differentiation factors. Cell. 1987 May 22;49(4):437–438. doi: 10.1016/0092-8674(87)90443-0. [DOI] [PubMed] [Google Scholar]
  22. McCune B. K., Mullin B. R., Flanders K. C., Jaffurs W. J., Mullen L. T., Sporn M. B. Localization of transforming growth factor-beta isotypes in lesions of the human breast. Hum Pathol. 1992 Jan;23(1):13–20. doi: 10.1016/0046-8177(92)90004-m. [DOI] [PubMed] [Google Scholar]
  23. Mizukami Y., Tajiri K., Nonomura A., Noguchi M., Taniya T., Koyasaki N., Nakamura S., Matsubara F. Effects of tamoxifen, medroxyprogesterone acetate and estradiol on tumor growth and oncogene expression in MCF-7 breast cancer cell line transplanted into nude mice. Anticancer Res. 1991 May-Jun;11(3):1333–1338. [PubMed] [Google Scholar]
  24. Roberts A. B., Flanders K. C., Heine U. I., Jakowlew S., Kondaiah P., Kim S. J., Sporn M. B. Transforming growth factor-beta: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci. 1990 Mar 12;327(1239):145–154. doi: 10.1098/rstb.1990.0050. [DOI] [PubMed] [Google Scholar]
  25. Roberts A. B., Flanders K. C., Kondaiah P., Thompson N. L., Van Obberghen-Schilling E., Wakefield L., Rossi P., de Crombrugghe B., Heine U., Sporn M. B. Transforming growth factor beta: biochemistry and roles in embryogenesis, tissue repair and remodeling, and carcinogenesis. Recent Prog Horm Res. 1988;44:157–197. doi: 10.1016/b978-0-12-571144-9.50010-7. [DOI] [PubMed] [Google Scholar]
  26. Roberts A. B., Sporn M. B. Regulation of endothelial cell growth, architecture, and matrix synthesis by TGF-beta. Am Rev Respir Dis. 1989 Oct;140(4):1126–1128. doi: 10.1164/ajrccm/140.4.1126. [DOI] [PubMed] [Google Scholar]
  27. Roberts A. B., Thompson N. L., Heine U., Flanders C., Sporn M. B. Transforming growth factor-beta: possible roles in carcinogenesis. Br J Cancer. 1988 Jun;57(6):594–600. doi: 10.1038/bjc.1988.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Salomon D. S., Ciardiello F., Valverius E., Saeki T., Kim N. Transforming growth factors in human breast cancer. Biomed Pharmacother. 1989;43(9):661–667. doi: 10.1016/0753-3322(89)90084-x. [DOI] [PubMed] [Google Scholar]
  29. Thompson A. M., Kerr D. J., Steel C. M. Transforming growth factor beta 1 is implicated in the failure of tamoxifen therapy in human breast cancer. Br J Cancer. 1991 Apr;63(4):609–614. doi: 10.1038/bjc.1991.140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Thompson A. M., Steel C. M., Foster M. E., Kerr D., Paterson D., Deane D., Hawkins R. A., Carter D. C., Evans H. J. Gene expression in oestrogen-dependent human breast cancer xenograft tumours. Br J Cancer. 1990 Jul;62(1):78–84. doi: 10.1038/bjc.1990.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Travers M. T., Barrett-Lee P. J., Berger U., Luqmani Y. A., Gazet J. C., Powles T. J., Coombes R. C. Growth factor expression in normal, benign, and malignant breast tissue. Br Med J (Clin Res Ed) 1988 Jun 11;296(6637):1621–1624. doi: 10.1136/bmj.296.6637.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Walker R. A., Dearing S. J. Transforming growth factor beta 1 in ductal carcinoma in situ and invasive carcinomas of the breast. Eur J Cancer. 1992;28(2-3):641–644. doi: 10.1016/s0959-8049(05)80116-9. [DOI] [PubMed] [Google Scholar]
  33. Welch D. R., Fabra A., Nakajima M. Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7678–7682. doi: 10.1073/pnas.87.19.7678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zugmaier G., Ennis B. W., Deschauer B., Katz D., Knabbe C., Wilding G., Daly P., Lippman M. E., Dickson R. B. Transforming growth factors type beta 1 and beta 2 are equipotent growth inhibitors of human breast cancer cell lines. J Cell Physiol. 1989 Nov;141(2):353–361. doi: 10.1002/jcp.1041410217. [DOI] [PubMed] [Google Scholar]

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

RESOURCES