Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells

Cavaillès, Vincent; Augereau, Patrick; Garcia, Marcel; Rochefort, Henri

doi:10.1093/nar/16.5.1903

Cited by 119 publications

(52 citation statements)

References 26 publications

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“…RIA for cathepsin D. The commercially available ELSA cath-D kit consisted of ELSA tubes coated with the anti-cathepsin-D monoclonal antibody (8,39); 300 l of monoclonal 125 I-labeled anti-cathepsin-D antibody and then 50 l of sample (medium or cytosolic extract) were added to each tube. This mixture was then incubated at 25ЊC with shaking in an incubator shaker for 3 h. The tubes were then washed three times with 3 ml of Tween 20 solution after the contents in the tube were removed by aspiration.…”

Section: Chemicalsmentioning

confidence: 99%

Molecular Mechanism of Inhibition of Estrogen-Induced Cathepsin D Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in MCF-7 Cells

Krishnan

Porter

Santostefano

et al. 1995

Molecular and Cellular Biology

190

121

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17␤-Estradiol (E2) induces cathepsinThe aryl hydrocarbon (Ah) receptor protein is expressed in laboratory animals and humans and in mammalian cells in culture (54,65). Although the endogenous ligand(s) for this receptor has not been identified, several different classes of compounds reversibly bind the Ah receptor, and these include the polynuclear and polyhalogenated aromatic hydrocarbons (42,54,57,59,65,67). 3-Methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are prototypical aromatic hydrocarbons which exhibit high-affinity binding (K d Յ 1 nM) for the Ah receptor (44, 58) and have been utilized for characterizing Ah receptor-mediated responses.TCDD induces a broad spectrum of biochemical and toxic responses including a wasting syndrome, immune suppression, hepatotoxicity, developmental and reproductive toxicity, carcinogenicity, dermal toxicity, alteration of endocrine response pathways, and modulation of diverse enzyme activities (26,29,59,73,82). The induction of CYP1A1 gene expression by TCDD and 3-methylcholanthrene has been extensively investigated, and the results indicate that the Ah receptor acts as a nuclear ligand-induced transcription factor (13,29,73,82).After treatment of animals or cells with TCDD, there is a rapid formation of a heterodimeric nuclear Ah receptor complex (19) which consists of the ligand-binding protein (7) and the Ah receptor nuclear translocator (Arnt) protein (31). The unbound Ah receptor is associated with heat shock protein 90 (48,55,60,61), and the subcellular distribution of these proteins in the absence of ligand is currently being investigated (60, 61). The nuclear Ah receptor complex interacts with cognate genomic sequences (dioxin or xenobiotic responsive elements [DREs and XREs, respectively]) in the 5Ј-promoter region of the CYP1A1 gene and transactivates CYP1A1 gene expression (15-17, 27, 34, 70, 83). There is evidence that this transactivation process is comparable for induction of CYP1A1 gene expression and induction of the expression of other members of the Ah gene battery, namely CYP1A2, glucuronosyl transferase, aldehyde-3-dehydrogenase, glutathione S-transferase Ya gene, and NAD(P)H:menadione oxidoreductase (1,35,53,56,62,64). Other studies also report that enhanced expression of other genes by TCDD is due to posttranscriptional processes (20).TCDD also decreases gene expression and/or the respective activities of the encoded proteins. Phosphoenolpyruvate carboxy kinase, glucose-6-phosphatase, and tryptophan 2,3-dioxygenase activities and mRNA levels are decreased in rats treated with an acutely toxic dose (125 g/kg of body weight) of TCDD (72). Rat uterine c-fos and epidermal growth factor * Corresponding author. Mailing address: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843-4466.

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Section: Chemicalsmentioning

confidence: 99%

Molecular Mechanism of Inhibition of Estrogen-Induced Cathepsin D Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in MCF-7 Cells

Krishnan

Porter

Santostefano

et al. 1995

Molecular and Cellular Biology

190

121

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“…Bergeron et al (10) studied extensively as an in vitro and in vivo model of estrogen-dependent breast cancer and displays multiple estrogendependent gene expressions (15). Estrogendependent preconfluent cell proliferation in specific strains has been used as a marker for estrogenicity (16).…”

Section: Introductionmentioning

confidence: 99%

Lack of Synergy by Mixtures of Weakly Estrogenic Hydroxylated Polychlorinated Biphenyls and Pesticides

Arcaro¹,

Vakharia²,

Yang³

et al. 1998

Environmental Health Perspectives

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We examined the estrogenicity of binary mixtures of the hydroxylated polychlorinated biphenyls (OHPCBs) 2,4,6-trichloro-4'-biphenylol (2,4,6-TCB-4'-OH) and 2,3,4,5,-tetrachloro-4'-biphenylol and the pesticides endosulfan and dieldrin. The OHPCBs and pesticides were tested in both the MCF-7 focus assay and a competitive estrogen-receptor binding assay. Although the individual OHPCBs were estrogenic in both assays, there was no synergy when they were combined at various concentrations as equimolar mixtures. Of the pesticides, only endosulfan was estrogenic. Its weak estrogenicity was seen only in the MCF-7 focus assay at the highest concentration tested-10 pM. There was no synergy of the equimolar mixture of pesticides. To determine whether OHPCBs might respond synergistically when combined with the natural estrogen 17-estradiol (E2), we tested various concentrations of 2,4,6-TCB-4'-OH in the MCF-7 focus assay in combination with physiologically relevant concentrations of E2. There was no synergy between 2,4,6-TCB-4'-OH and E2. Pretreatment for 3 or 7 days with 2,4,6-TCB-4'-OH had no effect on subsequent foci induced by a combination of 2,4,6-TCB-4'-OH and E2. Although our results showing no synergy between the pesticides or the OHPCBs are in contrast to a recent report that binary mixtures of these same compounds produce synergistic responses in estrogen-sensitive assays, they are in agreement with the results from other assays showing a lack of synergy. Considering all results, it appears that synergy of these weakly estrogenic compounds acting through the estrogen receptor is unlikely.

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“…We tested ERa, shown to be downregulated by E2, and progesterone receptor (PgR), Cathepsin D and pS2, all of which have been shown to be upregulated by E2 in MCF-7 cells (Read et al, 1989;Nardulli et al, 1988;Cavailles et al, 1988;Weaver et al, 1988). We have previously demonstrated that the loss of PgR regulation by E2 attests for the loss of ER function Saceda et al, 1996).…”

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confidence: 99%

Cyr61 promotes breast tumorigenesis and cancer progression

et al. 2002

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Cyr61, a member of the CCN family of genes, is an angiogenic factor. We have shown that it is overexpressed in invasive and metastatic human breast cancer cells and tissues. Here, we investigated whether Cyr61 is necessary and/or sufficient to bypass the 'normal' estrogen (E2) requirements for breast cancer cell growth. Our results demonstrate that Cyr61 is sufficient to induce MCF-7 cells to grow in the absence of E2. Cyr61-transfected MCF-7 cells (MCF-7/Cyr61) became E2-independent but still E2-responsive. On the other hand, MCF-7 cells transfected with the vector DNA (MCF-7/V) remain E2-dependent. MCF-7/Cyr61 cells acquire an antiestrogen-resistant phenotype, one of the most common clinical occurrences during breast cancer progression. MCF-7/Cyr61 cells are anchorageindependent and capable of forming Matrigel outgrowth patterns in the absence of E2. ERa expression in MCF-7/Cyr61 cells is decreased although still functional. Moreover, MCF-7/Cyr61 cells are tumorigenic in ovariectomized athymic nude mice. The tumors resemble human invasive carcinomas with increased vascularization and overexpression of vascular endothelial growth factor (VEGF). Our results demonstrate that Cyr61 is a tumor-promoting factor and a key regulator of breast cancer progression. This study provides evidence that Cyr61 is sufficient to induce E2-independence and antiestrogen-resistance, and to promote invasiveness in vitro, and to induce tumorigenesis in vivo, all of which are characteristics of an aggressive breast cancer phenotype.

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Estrogens and growth factors induce the mRNA of the 52K-pro-cathepsin-D secreted by breast cancer cells

Cited by 119 publications

References 26 publications

Molecular Mechanism of Inhibition of Estrogen-Induced Cathepsin D Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in MCF-7 Cells

Molecular Mechanism of Inhibition of Estrogen-Induced Cathepsin D Gene Expression by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) in MCF-7 Cells

Lack of Synergy by Mixtures of Weakly Estrogenic Hydroxylated Polychlorinated Biphenyls and Pesticides

Cyr61 promotes breast tumorigenesis and cancer progression

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