RGD Reference Report - Transforming growth factor beta 1 is implicated in the failure of tamoxifen therapy in human breast cancer. - Rat Genome Database

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

Authors: Thompson, AM  Kerr, DJ  Steel, CM 
Citation: Thompson AM, etal., Br J Cancer. 1991 Apr;63(4):609-14.
RGD ID: 7394824
Pubmed: PMID:2021547   (View Abstract at PubMed)
PMCID: PMC1972347   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
breast cancer treatmentIEP 7394824 RGD 
breast cancer treatmentISOTGFB1 (Homo sapiens)7394824; 7394824 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tgfb1  (transforming growth factor, beta 1)

Genes (Mus musculus)
Tgfb1  (transforming growth factor, beta 1)

Genes (Homo sapiens)
TGFB1  (transforming growth factor beta 1)


Additional Information