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PMID: 2021547 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transforming growth factor beta 1 is implicated in the failure of tamoxifen therapy in human breast cancer.

British journal of cancer ·Vol. 63 ·No. 4 ·1991-04-00 ·Pages 609-14

Thompson AM, Kerr DJ, Steel CM

Abstract

Transforming growth factor-beta 1 (TGF-beta 1) is inhibitory for breast epithelial cells in vitro and treatment of breast cancer cell lines with tamoxifen results in a rise in TGF-beta 1 mRNA expression with associated inhibition of cell growth. To study whether these findings apply in vivo we examined TGF-beta 1 mRNA expression in an oestrogen-dependent mouse xenograft system following systemic treatment of the mice with tamoxifen. In agreement with in vitro studies. TGF-beta 1 mRNA expression was sustained at high levels and associated with a reduction in tumour size. A subsequent study of breast tumour tissue from 56 patients demonstrated high levels of TGF-beta 1 mRNA in 45 of the tumours. High expression was found to correlate with premenopausal status, but not with tumour oestrogen receptor content or other parameters. In a subgroup of 11 patients who had received tamoxifen therapy for 3 to 6 months prior to surgery, unexpectedly high levels of TGF-beta 1 mRNA were demonstrated in tumours increasing in size and unresponsive to tamoxifen. Data from this study indicate that in patients with breast cancer, TGF-beta 1 in the tumour may not behave as in vitro and xenograft studies have suggested. We speculate that failure of tamoxifen therapy may be due to failure of the autocrine inhibitory functions of TGF-beta 1 either alone or in combination with paracrine stimulation of stromal cells or angiogenesis and localised immunosuppression. Further studies of active TGF-beta 1, TGF-beta receptors and the interactions with other growth factors will be required to elucidate the precise role of TGF-beta 1 in human breast cancer and in the failure of tamoxifen therapy.

MeSH Terms
Adult Aged Aged, 80 and over Animals Breast Neoplasms/drug therapy,genetics Estrogens/physiology Female Humans Mice Mice, Inbred CBA Middle Aged Neoplasm Transplantation Neoplasms, Hormone-Dependent/drug therapy,genetics RNA, Messenger/analysis RNA, Neoplasm/analysis Tamoxifen/therapeutic use Transforming Growth Factor beta/genetics
Chemicals
Estrogens RNA, Messenger RNA, Neoplasm Transforming Growth Factor beta Tamoxifen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Thompson A M
Department of Surgery, Royal Infirmary, Edinburgh, UK.
Kerr D J
Steel C M
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Article Info
Journal
British journal of cancer
Abbr.
Br J Cancer
ISSN
0007-0920
DOI
10.1038/bjc.1991.140
Published
1991-04-00
Pages
609-14
Language
English
Region
England
NLM ID
0370635
PMCID
PMC1972347
Subset
IM
External Links
PubMed source DOI: 10.1038/bjc.1991.140 PMC Full Text View journal details
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