Anti-oestrogens Induce the Secretion of Active Transforming Growth Factor Beta from Human Fetal Fibroblasts

Overview

Journal Br J Cancer

Specialty Oncology

Date 1990 Sep 1

PMID 1698443

Citations 51

Authors

A A Colletta

L M Wakefield

F V Howell

K E Van Roozendaal

D Danielpour

S R Ebbs

M B Sporn

M Baum

Affiliations

Soon will be listed here.

Abstract

The clinical use of anti-oestrogens in breast cancer therapy has traditionally been restricted to tumours that contain measurable oestrogen receptor protein. However, it is now widely recognised that the clinical response to adjuvant anti-oestrogen therapy appears to be independent of the oestrogen receptor content of the primary tumour. The study reported here was designed to investigate the possibility that human stromal cells can respond to anti-oestrogens by an increased synthesis of the inhibitory growth factor, transforming growth factor beta (TGF-beta). Two established human fetal fibroblast strains were used as models for the breast cancer stromal fibroblasts. These cells were found to respond to the addition of anti-oestrogens by a large increase in their synthesis of biologically active TGF-beta. Despite the application of ligand binding, immunoassay and Northern analysis, no oestrogen receptor or oestrogen receptor mRNA was detected in either of the human fetal fibroblasts strains. These observations may provide a mechanism of action of anti-oestrogens that is independent of the presence of oestrogen receptor in the tumour epithelial cells, and thus provide an explantation for the counter-intuitive results of adjuvant anti-oestrogen action.

Citing Articles

Conservative treatment of Peyronie's disease: a guide.

Cosentino M, Di Nauta M, Boeri L, Ferraioli G, Lucignani G, Ricapito A World J Urol. 2024; 42(1):317.

PMID: 38740620 DOI: 10.1007/s00345-024-04975-6.

Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.

Danielpour D Pharmaceuticals (Basel). 2024; 17(4).

PMID: 38675493 PMC: 11054419. DOI: 10.3390/ph17040533.

Regulation of aromatase in cancer.

Molehin D, Rasha F, Layeequr Rahman R, Pruitt K Mol Cell Biochem. 2021; 476(6):2449-2464.

PMID: 33599895 DOI: 10.1007/s11010-021-04099-0.

Effect of Adjuvant Hormonal Therapy on the Development of Pulmonary Fibrosis after Postoperative Radiotherapy for Breast Cancer.

Anzic M, Marinko T J Breast Cancer. 2020; 23(5):449-459.

PMID: 33154822 PMC: 7604379. DOI: 10.4048/jbc.2020.23.e48.

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.

Meehan J, Gray M, Martinez-Perez C, Kay C, Pang L, Fraser J Front Oncol. 2020; 10:628.

PMID: 32391281 PMC: 7193869. DOI: 10.3389/fonc.2020.00628.

References

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Knabbe C, Lippman M, Wakefield L, Flanders K, Kasid A, Derynck R . Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987; 48(3):417-28. DOI: 10.1016/0092-8674(87)90193-0. View

Haggie J, SELLWOOD R, Howell A, Birch J, Schor S . Fibroblasts from relatives of patients with hereditary breast cancer show fetal-like behaviour in vitro. Lancet. 1987; 1(8548):1455-7. DOI: 10.1016/s0140-6736(87)92206-9. View

Jakowlew S, Dillard P, Sporn M, Roberts A . Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming growth factor beta 4 from chicken embryo chondrocytes. Mol Endocrinol. 1988; 2(12):1186-95. DOI: 10.1210/mend-2-12-1186. View

Kondaiah P, Van Obberghen-Schilling E, Ludwig R, Dhar R, Sporn M, Roberts A . cDNA cloning of porcine transforming growth factor-beta 1 mRNAs. Evidence for alternate splicing and polyadenylation. J Biol Chem. 1988; 263(34):18313-7. View

Murphy L, Dotzlaw H . Variant estrogen receptor mRNA species detected in human breast cancer biopsy samples. Mol Endocrinol. 1989; 3(4):687-93. DOI: 10.1210/mend-3-4-687. View

Danielpour D, Dart L, Flanders K, Roberts A, Sporn M . Immunodetection and quantitation of the two forms of transforming growth factor-beta (TGF-beta 1 and TGF-beta 2) secreted by cells in culture. J Cell Physiol. 1989; 138(1):79-86. DOI: 10.1002/jcp.1041380112. View

Wakefield L, Smith D, Masui T, Harris C, Sporn M . Distribution and modulation of the cellular receptor for transforming growth factor-beta. J Cell Biol. 1987; 105(2):965-75. PMC: 2114751. DOI: 10.1083/jcb.105.2.965. View

Giguere V, Yang N, Segui P, Evans R . Identification of a new class of steroid hormone receptors. Nature. 1988; 331(6151):91-4. DOI: 10.1038/331091a0. View

10.

Pircher R, Lawrence D, Jullien P . Latent beta-transforming growth factor in nontransformed and Kirsten sarcoma virus-transformed normal rat kidney cells, clone 49F. Cancer Res. 1984; 44(12 Pt 1):5538-43. View

11.

Lawrence D, Pircher R, Jullien P . Normal embryo fibroblasts release transforming growth factors in a latent form. J Cell Physiol. 1984; 121(1):184-8. DOI: 10.1002/jcp.1041210123. View

12.

Horgan K, Jones D, Mansel R . Mitogenicity of human fibroblasts in vivo for human breast cancer cells. Br J Surg. 1987; 74(3):227-9. DOI: 10.1002/bjs.1800740326. View

13.

Iqbal M, Corbishley T, Wilkinson M, Williams R . A microassay for the determination of binding parameters of estrogen and androgen receptors employing affinity immobilization on Cibacron blue 3GA-Sepharose 6B. Anal Biochem. 1985; 144(1):79-85. DOI: 10.1016/0003-2697(85)90086-7. View

14.

Feinberg A, Vogelstein B . A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983; 132(1):6-13. DOI: 10.1016/0003-2697(83)90418-9. View

15.

Gleiber W, Schiffmann E . Identification of a chemoattractant for fibroblasts produced by human breast carcinoma cell lines. Cancer Res. 1984; 44(8):3398-402. View

16.

Watts C, Murphy L, Sutherland R . Microsomal binding sites for nonsteroidal anti-estrogens in MCF 7 human mammary carcinoma cells. Demonstration of high affinity and narrow specificity for basic ether derivatives of triphenylethylene. J Biol Chem. 1984; 259(7):4223-9. View

17.

Sutherland R . Estrogen antagonists in chick oviduct: antagonist activity of eight synthetic triphenylethylene derivatives and their interactions with cytoplasmic and nuclear estrogen receptors. Endocrinology. 1981; 109(6):2061-8. DOI: 10.1210/endo-109-6-2061. View

18.

Jordan V, Collins M, Rowsby L, Prestwich G . A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol. 1977; 75(2):305-16. DOI: 10.1677/joe.0.0750305. View

19.

Skidmore J, WALPOLE A, Woodburn J . Effect of some triphenylethylenes on oestradiol binding in vitro to macromolecules from uterus and anterior pituitary. J Endocrinol. 1972; 52(2):289-98. DOI: 10.1677/joe.0.0520289. View

20.

Ten Dijke P, Hansen P, Iwata K, Pieler C, Foulkes J . Identification of another member of the transforming growth factor type beta gene family. Proc Natl Acad Sci U S A. 1988; 85(13):4715-9. PMC: 280506. DOI: 10.1073/pnas.85.13.4715. View