Clinical Relevance of T1-S, an Oncogene-Inducible, Secreted Glycoprotein of the Immunoglobulin Superfamily, in Node-Negative Breast Cancer

Prechtel, Dieter; Harbeck, Nadia; Berger, Ursula; Höfler, Heinz; Werenskiold, Ann Katrin

doi:10.1038/labinvest.3780223

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…However, interestingly, two homozygous knockout mice spontaneously developed what appeared to be subcutaneous tumors on their neck and trunk and a third animal was found moribund due to unknown causes (not shown). Possibly relevant to these observations are previous findings that sST2 is correlated with progression of breast cancer [15] and that sST2 may modulate tumor cell activity in vitro [16].…”

Section: Introductionmentioning

confidence: 55%

Deletion of the ST2 proximal promoter disrupts fibroblast‐specific expression but does not reduce the amount of soluble ST2 in circulation

Lipsky

Toy²,

Swart³

et al. 2012

Eur J Immunol

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IL-33 signals through ST2, which is expressed either as a full-length signaling receptor or a truncated soluble receptor that can suppress IL-33 activity. Previous data suggest that soluble ST2 mRNA in fibroblasts is coupled to a serum-inducible proximal promoter, while full-length ST2 expression in immune cells is directed from a distal promoter. In order to better understand the function of the alternative promoters and how they ultimately affect the regulation of IL-33, we generated a mouse in which the ST2 proximal promoter is deleted. Promoter deletion had no impact on ST2 expression in mast cells or their ability to respond to IL-33. In contrast, it resulted in a complete loss of both soluble and full-length ST2 mRNA in fibroblasts, which corresponded with both an inability to secrete soluble ST2 and a defect in IL-33 responsiveness. Importantly, in spite of the fibroblast defect, soluble ST2 concentrations were not reduced in the serum of naïve or allergenexposed knockout mice. In summary, we found that ST2 promoter usage is largely celltype dependent but does not dictate splicing. Moreover, the proximal promoter is not a major driver of circulating soluble ST2 under the conditions tested.

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Section: Introductionmentioning

confidence: 55%

Deletion of the ST2 proximal promoter disrupts fibroblast‐specific expression but does not reduce the amount of soluble ST2 in circulation

Lipsky

Toy²,

Swart³

et al. 2012

Eur J Immunol

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“…25 ST2 expression is increased in situ in breast cancer and is associated with reduced disease progression. 26 These findings suggest that confounding systemic inflammatory/immune diseases have the potential to complicate the predictive value of serum ST2 measurements in heart failure, although at the present time, asthma and some autoimmune diseases are the only diseases other than heart failure in which an increase in serum ST2 has been identified. We recently found that ST2 levels were acutely increased in the serum of patients 1 day after myocardial infarction, positively correlated with creatine kinase levels, and inversely correlated with ejection fraction.…”

Section: Discussionmentioning

confidence: 94%

Identification of Serum Soluble ST2 Receptor as a Novel Heart Failure Biomarker

et al. 2003

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Background-Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation. Methods and Results-Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (rϭ0.36, PϽ0.0001), baseline proatrial natriuretic peptide (ProANP) levels (rϭ0.36, PϽ0.0001), and baseline norepinephrine levels (rϭ0.39, PϽ0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (Pϭ0.048), as was baseline BNP (PϽ0.0001) and baseline ProANP (PϽ0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP. Conclusions-Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.

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“…Recent data on the expression of ST2, the human homologue to T1, in human breast cancers are somewhat conflicting, however. The secreted ST2‐S form was overexpressed in two‐thirds of patients with lymph node–negative breast cancers associated with a high to moderate level of differentiation of the tumors [56] and with a longer disease‐free survival period [57].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells

González‐Sancho

Figueroa

López-Barahona

et al. 2002

Molecular Carcinogenesis

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The relationship between thyroid hormone (triiodothyronine, T(3)) and breast cancer is unclear. We studied the effect of the c-erbA/TR alpha proto-oncogene encoding a functional T(3) receptor (TR alpha 1), of its ligand T(3), and of its retroviral, mutated counterpart, the v-erbA oncogene, on the proliferation capacity of nontumorigenic mammary epithelial cells (EpH4). We found that EpH4 cells expressing ectopically TR (EpH4 + TR alpha 1) or v-erbA (EpH4 + v-erbA) proliferated faster than parental EpH4 cells that contained low levels of endogenous TR. T(3) inhibited DNA synthesis and proliferation in EpH4 + TR alpha 1 cells but not EpH4 or EpH4 + v-erbA cells. The study of cell-cycle genes showed that T(3) decreased cyclin D1 RNA and protein levels in EpH4 + TR alpha 1 cells. In addition, T(3) downregulated the expression of T1, a gene that is overexpressed in human breast adenocarcinomas and is induced by mitogens, serum, and several oncogenes and cytokines. Inhibition of the T1 gene by T(3) required both de novo mRNA and protein synthesis. Furthermore, T(3) abolished the induction of T1 by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and inhibited the activity of an activation protein 1-dependent promoter (-73-Col-CAT) in EpH4 + TR alpha 1 cells, suggesting that interference with activation protein 1 transcription factor plays a part in the inhibition of the T1 gene. Our results showed that T(3) reduced the proliferation of mammary epithelial cells and inhibited the expression of cyclin D1 and T1 genes.

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Clinical Relevance of T1-S, an Oncogene-Inducible, Secreted Glycoprotein of the Immunoglobulin Superfamily, in Node-Negative Breast Cancer

Cited by 9 publications

References 23 publications

Deletion of the ST2 proximal promoter disrupts fibroblast‐specific expression but does not reduce the amount of soluble ST2 in circulation

Deletion of the ST2 proximal promoter disrupts fibroblast‐specific expression but does not reduce the amount of soluble ST2 in circulation

Identification of Serum Soluble ST2 Receptor as a Novel Heart Failure Biomarker

Inhibition of proliferation and expression of T1 and cyclin D1 genes by thyroid hormone in mammary epithelial cells

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