The prognostic significance of transforming growth factors in human breast cancer

Murray, P; Barrett-Lee, Peter; Travers, Maureen T.; Luqmani, Yunus A.; Powles, T. J.; Coombes, R. Charles

doi:10.1038/bjc.1993.261

Cited by 73 publications

(29 citation statements)

References 29 publications

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“…However, we observed an interesting association between TGF-β expression and survival, since patients with TGF-β mRNA expression had a significantly better prognosis than patients who did not express this cytokine. Similar results were obtained also in breast carcinomas where the expression of TGF-β was associated with a longer disease-free interval (Murray et al, 1993) and with absence of nodal metastatic involvement. There is some evidence that the metastatic behaviour of a tumour is strongly determined by its ability to break down the basement membrane, possibly by the increased production of collagenase (Liotta et al, 1991).…”

Section: Tgf-β Expressionsupporting

confidence: 83%

“…Growth factors of the transforming growth factor beta family (TGF-β) have been reported as multifunctional growth factors and are synthesized by a wide variety of both normal and malignant cells (Derynk et al, 1985). TGF-β has multiple actions (Fajardo et al, 1996) and, owing to its highly potent inhibition function on cell growth (Ueki et al, 1992), many studies have evaluated the prognostic significance of the expression of this factor, especially in breast cancer (Murray et al, 1993;Auvinen et al, 1995), but only limited and confusing data are available at the moment.…”

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confidence: 99%

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Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

et al. 2000

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Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-α and TGF-β mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-α and TGF-β mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan–Meier analysis. In the univariate analysis patients without nodal metastatic involvement ( P = 0.02), less advanced tumour stage ( P = 0.02) or TNF-α and TGF-β positive cancers ( P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl -2 expression, we investigated the putative relation between TNF-α and TGF-β on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl -2 protein expression, on the other hand. Our results showed a significant direct association between TNF-α and bcl -2 ( P = 0.05) and an inverse association between TNF-α and microvessel count ( P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl -2 protein expression and vascular count ( P = 0.05), suggesting that the favourable effect of TNF-α on clinical outcome may be related to a bcl -2-mediated low neovascular development. © 2000 Cancer Research Campaign

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Section: Tgf-β Expressionsupporting

confidence: 83%

mentioning

confidence: 99%

Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

et al. 2000

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“…The method of mRNA measurement may be applicable in other organ disorders, as has been hypothesized and found for instance in the liver (44), the lungs (45), the heart (46), and in cancer research (47,48). In conclusion, the extent of histologic damage is negatively correlated with the GFR at time of biopsy, but it does not predict the rate of change in GFR after taking of the biopsy.…”

Section: Discussionmentioning

confidence: 85%

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

Eikmans¹,

Baelde²,

Hagen

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Molecular biologic techniques are currently considered as new diagnostic and prognostic parameters with a sensitivity and specificity exceeding those of histologic and functional data currently used in clinical practice. The results in various clinical settings have been of limited value up to now. This study is an investigation of the use of tissue levels of RNA determined in routine clinical kidney biopsies as prognostic tools. The focus was on RNA encoding for molecules known to be involved in the pathogenesis of renal disorders. Fresh kidney biopsy tissue was obtained from 52 patients with various renal diseases. The GFR was followed for 12 mo. The extent of glomerulosclerosis and interstitial fibrosis in the biopsies was determined with quantitative digital image analysis. Glomerular and tubulointerstitial compartments from each biopsy specimen were separated, and mRNA levels of TGF-␤, collagen I, collagen IV, and fibronectin were quantitated by real-time PCR. Correlations, along with 95% confidence intervals (CI), between all variables tested at time biopsy were determined. To assess their prognostic value, these variables were correlated with the slope of GFR within several time intervals after biopsy. In addition, to evaluate the predictive value of the variables for outcome in individual patients, differences for each variable were tested between patients showing progressive decline in renal function (slope GFR Ͻ 0) and patients showing stable or improving renal function over time (slope GFR Ն 0). In chronic renal diseases, the extent of histologic damage correlated with the GFR at the time of biopsy (r ϭ Ϫ0.44; CI Ϫ0.68 to Ϫ0.11), but it did not correlate with the slope expressing a change in GFR after the biopsy. Tubulointerstitial TGF-␤ mRNA levels correlated with the rate of change in GFR between time of biopsy and 1 mo later (r ϭ 0.41; CI, 0.07 to 0.67). The GFR at the time of biopsy correlated with the slope of change in GFR between time of biopsy and 12 mo later (r ϭ Ϫ0.50; CI, Ϫ0.73 to Ϫ0.18). In chronic renal diseases, glomerular fibronectin mRNA levels, in comparison with the GFR at time of biopsy, correlated relatively strongly with the slope of change in GFR between 3 and 12 mo (r ϭ 0.50; CI, 0.16 to 0.74). Patients with favorable renal outcome after 12 mo showed significantly higher TGF-␤ mRNA levels and lower proteinuria levels at time of biopsy (P Ͻ 0.05) than patients with a progressive decline in renal function. This study shows that mRNA levels measured in kidney biopsies can function as prognostic tools in human renal diseases. In particular, relatively high levels of tubulointerstitial TGF-␤ mRNA and glomerular fibronectin mRNA are associated with less deterioration in renal function.

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“…Such a TGFbdependent increase of the cytotoxic efficiency of drugs may contribute to the efficiency of patient treatment. This mechanism, together with other effects of TGFb, such as growth inhibition, can explain the fact that intact TGFb/Smad signaling in tumor cells correlates with longer survival of patients with breast cancer (Muray et al, 1993;Xie et al, 2002), colorectal (Watanabe et al, 2001;Boulay et al, 2002) and advanced gastric (Xiangming et al, 2001) cancers, renal cell carcinoma (Miyajima et al, 2003) and ovarian cancer (Volodko et al, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

TGFβ1/Smad3 counteracts BRCA1-dependent repair of DNA damage

et al. 2005

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Inactivation of the BRCA1 gene has been found to confer susceptibility to early-onset familial breast and ovarian cancers. BRCA1 regulates DNA repair, chromatin remodeling and affects gene transcription. Transforming growth factor-b (TGFb) is a potent regulator of growth, apoptosis and invasiveness of tumor cells, including breast cancer cells. Here we show that Smad3 which is a component of the TGFb signaling pathway, forms a complex with BRCA1 in vitro and in vivo. The interaction is mediated by the MH1 domain of Smad3 and the Cterminal part of BRCA1. We observed a co-localization of Smad3 and BRCA1 in nuclear complexes. We also found that TGFb1/Smad3 counteracted BRCA1-dependent repair of DNA double-strand breaks in human breast epithelial cells, as evaluated by BRCA1 nuclear foci formation, single-cell gel electrophoresis and cell survival assays. Thus, TGFb1/Smad3 suppresses BRCA1-dependent DNA repair in response to a DNA damaging agent.

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The prognostic significance of transforming growth factors in human breast cancer

Abstract: Summary Transforming growth factor alpha (TGFa) and Transforming growth factor beta-I (TGF-P,)

Cited by 73 publications

References 29 publications

Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization

Renal mRNA Levels as Prognostic Tools in Kidney Diseases

TGFβ1/Smad3 counteracts BRCA1-dependent repair of DNA damage

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