Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells.

López-Barahona, Mònica; Fialka, Irene; González‐Sancho, José Manuel; Asunción, M.; González, Marcelo; Iglesias, Teresa; Bernal, Juan; Beug, Hartmut; Múñoz, Alberto

doi:10.1002/j.1460-2075.1995.tb07098.x

Cited by 47 publications

(32 citation statements)

References 61 publications

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“…In mouse EpH4 mammary epithelial cells expressing exogenous TRa1, T3 regulates expression of stromelysin-1 and -2, collagenase IVB, and tenascin-C and modulates the di erentiated phenotype (LoÂ pez- Barahona et al, 1995;GonzaÂ lez-Sancho et al, 1999). TR are also present in human breast cancer cell lines (Burke and McGuire, 1978;Zhou-Li et al, 1992), but con¯icting reports describe both mitogenic and antimitogenic e ects of T3 (Nogueira and Brentani, 1996;MartõÂ nez et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer

et al. 2002

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The relation between thyroid status and diseases and cancer is unclear. No detailed analysis of thyroid hormone receptor (TR) expression in human breast cancer has been reported. We have analysed the expression and mutational status of the TRa1, encoded by the c-erbA proto-oncogene, TRb1 and TRb2 isoforms in 70 sporadic breast cancers. Alterations in the RNA level of TRb1, TRa1, or both were found in a number of patients. No expression of TRb2 RNA was detected. Western blotting analysis con®rmed the di erences in expression at the protein level in those cases where su cient tumor sample was available. Additionally, tumor-speci®c truncated TRb1 RNA was found in six patients. Strikingly, three transcripts shared the same breakpoint. Only one tumor carried the corresponding deletion at the genomic DNA level, suggesting that the remaining abnormal TRb1 transcripts are aberrant splicing products. Though no signi®cant correlation was found between TRb1 alteration and any clinical parameter, it showed a tendency to associate with early age of onset (550 years). Our results reveal speci®c alterations in the expression of TRb and TRa genes in a subset of breast cancer patients, suggesting that deregulation of thyroid hormone target genes may be involved in the generation of this neoplasia.

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Section: Discussionmentioning

confidence: 99%

Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer

et al. 2002

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“…mental evidence for an increased number of thyroid receptors in spontaneous rat mammary tumors (42). In this respect, it is interesting to note that the expression and secretion of stromelysin-1, which promotes mammary carcinogenesis (43), is actually regulated by thyroid hormone in cells derived from the mammary gland (44). As st3 was originally isolated from breast cancer tissue, the possible role for thyroid hormone in the regulation of this gene in vivo cannot be excluded.…”

Section: Discussionmentioning

confidence: 99%

Multiple Regulatory Elements in the Murine Stromelysin-3 Promoter

Ludwig¹,

Basset²,

Anglard

2000

Journal of Biological Chemistry

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Stromelysin-3 (ST3) belongs to the matrix metalloproteinase (MMPs) family, a protease family involved in tissue remodeling. Although this family of enzymes is regulated by nuclear receptors, few hormone-responsive elements have been demonstrated in MMP promoters. In order to identify regulatory elements and/or factors that control the expression of the mouse st3 gene, we have analyzed genomic sequences encompassing 5 kilobase pairs of the ST3 promoter. Analysis of these sequences revealed several CCAAT/enhancer-binding proteins (C/EBP) and retinoic acid-responsive elements (RAREs), as well as one thyroid-responsive element. However, in contrast to most MMP promoters, no AP-1-binding sites were identified. Specific binding activities were demonstrated for all elements. Consistent with previous reports, retinoid X receptor is required for maximal binding to the ST3 RAREs and the TRE. The ST3-C/EBP element was shown to mediate dose-dependent promoter activation by C/EBP␤. Among the RAREs, the proximal DR1-RARE was shown to be sufficient for ST3 promoter activation by ligand-bound retinoid receptors, whereas the two distal DR2-RAREs appear to be involved more in the control of base-line promoter activity. Accordingly, ST3 expression was induced by retinoic acid and was reduced in cells where specific retinoic acid receptors had been inactivated. The involvement of these conserved regulatory elements is discussed in the context of physiological or pathological situations associated with st3 expression. Our findings therefore assign to C/EBP, retinoids, and thyroid hormone important roles in the regulation of ST3 gene expression.

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“…However, the presence of thyroid hormone receptors in human breast and breast cancer cell lines has been established (21,22,23,24), and the proliferative effect of T 3 has been confirmed by various experimental studies on breast cancer. Our findings are in line with these data (25,26,27,28).…”

Section: T 3 (Quartile)mentioning

confidence: 98%

Triiodothyronine levels in relation to mortality from breast cancer and all causes: a population-based prospective cohort study

Tosovic

Bondeson

et al. 2013

European Journal of Endocrinology

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Objective: The potential association between thyroid hormones and breast cancer has been investigated in a large number of studies without conclusive results. This study investigated triiodothyronine (T 3 ) levels in relation to breast cancer mortality in a population with no breast cancer patients at baseline. An additional aim was to study T 3 levels in relation to mortality from other cancers and all-cause mortality. Design and methods: This was a population-based prospective cohort study including 2185 women in whom T 3 levels were measured as part of a preventive health project, i.e. before diagnosis in women who later developed breast cancer. Mean follow-up was 24.1 years and record-linkage to The Swedish Cause-of-Death registry identified 471 women who died: 26 out of breast cancer and 182 from other cancers. Mortality was assessed using a Cox's analysis, yielding hazard ratios (HRs), with 95% confidence intervals. Analyses of T 3 as a continuous variable were repeated for pre-and peri/postmenopausal women separately. Results: T 3 levels were positively associated with the risk of breast cancer-specific death in the ageadjusted analysis: HR for T 3 as a continuous variable was 2.80 (1.26-6.25). However, the crude analysis did not reach statistical significance. Breast cancer mortality was even higher in postmenopausal women: 3.73 (1.69-8.22), but stratified analyses included few events. There were no statistically significant associations between T 3 levels and deaths from other cancers, age-adjusted HR: 1.09 (0.72-1.65) or all-cause mortality (1.25:0.97-1.60). Conclusions: This study, the first of its kind on prospectively measured T 3 levels, indicates that T 3 levels are positively associated with breast cancer-specific mortality and that this is not related to a general effect on all-cause mortality.

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Thyroid hormone regulates stromelysin expression, protease secretion and the morphogenetic potential of normal polarized mammary epithelial cells.

Cited by 47 publications

References 61 publications

Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer

Expression of thyroid hormone receptor/erbA genes is altered in human breast cancer

Multiple Regulatory Elements in the Murine Stromelysin-3 Promoter

Triiodothyronine levels in relation to mortality from breast cancer and all causes: a population-based prospective cohort study

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