Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells

Perry, Roger R.; Kang, Yuan; Greaves, Bridget

doi:10.1038/bjc.1995.527

Cited by 86 publications

(47 citation statements)

References 24 publications

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“…Increased synthesis of TGF-/31 is not associated with any concomitant elevation of mRNA levels in MCF-7 breast cancer cells (Knabbe et al, 1987) or fetal fibroblasts (Colletta et al, 1990). We have similar data from breast tumour fibroblasts in vitro (data not shown), and tamoxifen would therefore appear to enhance synthesis at a post-transcriptional level, although transcriptional mechanisms may also be operative depending on the local tissue levels of tamoxifen (Perry et al, 1995;Benson and Baum, 1996) and TGF-# isoform type (Arrick et al, 1994;MacCallum et al, 1994).…”

Section: Secretion Of Tgf-f3 Isoforms Into Conditioned Media Of Fibrosupporting

confidence: 61%

Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen

Benson

Wakefield²,

Baum³

et al. 1996

Br J Cancer

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Summary Tamoxifen may mediate its effect in early breast cancer in part via an oestrogen receptor (ER)-independent pathway by directly stimulating fibroblasts to produce the negative paracrine growth factor transforming growth factor (TGF)-f,. We have previously shown that secretion of this factor is induced 3-to 30-fold in human fetal fibroblasts in vitro, and by stromal fibroblasts in vivo following tamoxifen treatment of ERpositive and ER-negative breast cancer patients. Primary cultures of breast tumour fibroblasts have been exposed to tamoxifen for 48 h, and rates of secretion of TGF-fl, and TGF-fl2 measured using a quantitative immunoassay. Fibroblast strains derived from malignant and benign tumours produced and secreted similar amounts of TGF-flp, but benign breast tumour fibroblasts secreted significantly higher levels of TGF-f32 compared with fibroblasts of malignant origin. Tamoxifen did not induce any consistent increase in TGF-,B secretion into the conditioned medium, but immunofluorescence analysis for the intracellular form of TGF-f3, revealed evidence of increased immunoreactive protein in tamoxifen-treated fibroblasts, which is localised to the nucleus. Therefore synthesis of TGF-fl, appears to be stimulated by tamoxifen, but increased secretion may be abrogated in vitro. Furthermore, using immunocytochemistry and transient transfection with an ER-responsive reporter construct, no ER was demonstrable in these fibroblasts supporting the proposed ER-independent paracrine pathway.

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Section: Secretion Of Tgf-f3 Isoforms Into Conditioned Media Of Fibrosupporting

confidence: 61%

Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen

Benson

Wakefield²,

Baum³

et al. 1996

Br J Cancer

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“…Likewise, similar discrepancies have also been observed in cultured mammalian cells and in livers after partial hepatectomy. [10][11][12][13] Explanations for these discrepancies include that extensive post-transcriptional regulation may control the actual protein amount; e.g., retinoic acid prolongs the stability of the TGF-β 1 mRNA, whereas the anti-estrogen tamoxifen has been reported to reduce the translatability of the message. 11,12 There is strong evidence that the 5Ј-UTR region of the TGF-β 1 mRNA regulates expression of the protein by translational mechanisms in a cell-type specific manner.…”

Section: Discussionmentioning

confidence: 99%

“…The expression of TGF-β appears to be regulated partially at the post-transcriptional level, which emphasizes the importance of studying the message and the protein of this cytokine. [10][11][12][13][14] The function of this cytokine is dependent on the interaction with surface receptor types I, II, and III (TβRs I-III). TβR III is proposed to be involved in regulating the access of ligand to TβRs I and II.…”

mentioning

confidence: 99%

Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia

et al. 1998

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Transforming growth factor β 1 (TGF-β 1 ) has been implicated as inhibitor of cell proliferation and a potent inducer of apoptosis in vitro and in vivo after the administration of high doses. To assess the role of endogenous TGF-β 1 , we quantitated the cytokine and its receptors in rat liver during regenerative and hyperplastic growth, regression by apoptosis, and in hepatocellular carcinoma (HCC). This was accomplished by Northern blot analysis and by RNase protection assay of the messenger RNA (mRNA) of TGF-β 1 and TGF-β receptors (TβR) types I to III and by an activity bioassay of the TGF-β proteins. Untreated rat livers were found to contain 15.6 ؎ 4.8 ng TGF-β 1 protein/g tissue; TGF-β 2 protein was not detected. To induce toxic cell death and subsequent regenerative DNA synthesis in the liver, rats were treated with a necrogenic dose of carbon tetrachloride (CCl 4 ). After 24 and 48 hours, there was an upregulation of TGF-β 1 (mRNA, up to tenfold; protein, about twofold) and of TβRs (mRNA: two-to fourfold); that indicates an overall enhanced production of and sensitivity to TGF-β 1 , which may serve to confine the regenerative response. Hyperplastic liver growth and regression of the hyperplasia were induced by treatment with cyproterone acetate (CPA) or nafenopin (NAF) followed by withdrawal; neither mRNAs of TGF-β 1 and TβR types I to III nor TGF-β 1 protein exhibited significant changes during the growth phase or during regression by apoptosis. We also studied neoplastic growth. HCC, obtained after long-term treatment with NAF, exhibited high rates of cell replication and apoptosis. The majority of lesions contained mRNA and protein of TGF-β 1 and mRNA of TβR types I to III at concentrations similar to those of the surrounding tissue. In conclusion, during liver regeneration there is a pronounced upregulation of expression of both TGF-β 1 and TβRs I to III, but not during mitogen-induced liver growth or regression. It appears that apoptosis is induced via altered local concentration of TGF-β 1 in a paracrine and/or autocrine way. By this mechanism the lethal effects of TGF-β 1 may be locally confined, and overshoots of apoptosis in the liver may be prevented. (HEPATOLOGY 1998;28:717-726.)

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“…It has been reported that anti-oestrogen causes a G1-S blockade and induces apoptosis in ER-positive breast cancer cells (Perry et al, 1995;Watts et al, 1995). It is also suggested that a murine anti-HER2 antibody induces apoptosis in HER2-overexpressing cancer cells (Kita et al, 1996).…”

Section: mentioning

confidence: 99%

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

et al. 2000

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Summary Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, but most of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2 signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combined therapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect of combined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, on the cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combined treatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, but showed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, which express no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1-S blockade and apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for the treatment of patients with breast cancer expressing both ER and HER2.

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Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells

Cited by 86 publications

References 24 publications

Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen

Synthesis and secretion of transforming growth factor beta isoforms by primary cultures of human breast tumour fibroblasts in vitro and their modulation by tamoxifen

Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

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