Ets-1 activates parathyroid hormone-related protein gene expression in tumorigenic breast epithelial cells

Cataisson, Christophe; Gordon, Johnthan; Roussière, Mickael; Abdalkhani, Arman; Lindemannn, Ralph; Dittmer, Jürgen; Foley, John; Bouizar, Zhor

doi:10.1016/s0303-7207(02)00298-8

Cited by 21 publications

(45 citation statements)

References 35 publications

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“…P1 and P3 are canonical TATA promoters (Mangin et al, 1990;Campos et al, 1992;Suva et al, 1989) and initiate transcription at exons 1 and 4 respectively, while P2 is a GC-rich promoter that initiates transcription upstream of exon IC (Vasavada et al, 1993). Evaluation of PTHrP alternative promoter usage by qualitative (Southby et al, 1995 and and quantitative reverse transcription RT-PCR (Bouizar et al, 1999;Richard et al, 2003) revealed high concentrations of P3-initiated transcripts in most tumors, including breast cancers (Bouizar et al, 1999) and many tumor cell lines (Cataisson et al, 2003). The amino acid sequences encoded by only two of the 9 exons in the human gene are present in all transcripts.…”

Section: Gene Structurementioning

confidence: 99%

“…Therefore, the PTHrP gene seems to use mainly its downstream TATA (P3) and mid-region GC-rich (P2) promoters in breast cancers, especially in those that developed metastases (Bouizar et al 1999) (Figure2,3). The tumorigenic NS2T2A1 cells contained increased levels of the transcripts that encode for the 1-139 isoform and showed that the P3 promoter was most active in lines produced high levels of PTHrP mRNA (Cataisson et al, 2003) (Figure 2,3). GC-rich cis regulatory regions do not appear to be limited to a particular class of genes.…”

Section: Splicing Patterns Of Pthrp Mrnas In Breast Tumorsmentioning

confidence: 99%

“…2. Prevalence of PTHrP 139 and the P3 (TATA) promoter in invasive breast cancer and invasive breast cancer cell line (NS2T2A1) (Bouizar et al, 1999, Cataisson et al 2003.…”

Section: Splicing Patterns Of Pthrp Mrnas In Breast Tumorsmentioning

confidence: 99%

“…The Ets, SMAD, and Sp1 binding sites and a CRE-like site may be involved in the control of PTHrP gene expression in some cancer cell lines (Cataisson et al, 2003;Lindemann et al, 2001;Karperien et al, 1997;Chilco et al, 1998). Also, bone osteoclasts may mediate the release of TGF-β from the bone matrix in order to stimulate PTHrP gene expression in breast cancer cells , Guise et al, 2002.…”

Section: The P3 (Tata) Promoter In Pthrp Transcriptionmentioning

confidence: 99%

“…The Ets binding site of the PTHrP P3 promoter and the amount of Ets1 were crucial for PTHrP production by the most tumorigenic NS2T2A1 cells (Cataisson et al, 2003). However the precise mechanisms by which Ets1 activates PTHrP gene expression during tumor progression in breast cancer are unknown.…”

Section: Transcription Factors That Regulate the P3 Promotermentioning

confidence: 99%

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Parathyroid Hormone Related Protein: A Marker of Breast Tumor Progression and Outcome

Bouizar¹

2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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Section: Gene Structurementioning

confidence: 99%

Section: Splicing Patterns Of Pthrp Mrnas In Breast Tumorsmentioning

confidence: 99%

“…2. Prevalence of PTHrP 139 and the P3 (TATA) promoter in invasive breast cancer and invasive breast cancer cell line (NS2T2A1) (Bouizar et al, 1999, Cataisson et al 2003.…”

Section: Splicing Patterns Of Pthrp Mrnas In Breast Tumorsmentioning

confidence: 99%

Section: The P3 (Tata) Promoter In Pthrp Transcriptionmentioning

confidence: 99%

Section: Transcription Factors That Regulate the P3 Promotermentioning

confidence: 99%

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Parathyroid Hormone Related Protein: A Marker of Breast Tumor Progression and Outcome

Bouizar¹

2011

Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

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Inhibitor of DNA binding/differentiation 2 induced by hypoxia promotes synovial fibroblast–dependent osteoclastogenesis

Kurowska

Distler

Jüngel

et al. 2009

Arthritis & Rheumatism

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Objective. To map hypoxic areas in arthritic synovium and to establish the relevance of low oxygen levels to the phenotype of synovial fibroblasts, with special focus on bone degradation.Methods. To analyze the distribution of hypoxia in arthritic joints, the hypoxia marker EF5 was administered to mice with collagen-induced arthritis (CIA). To evaluate the effect of hypoxia on rheumatoid arthritis synovial fibroblasts (RASFs), reverse suppression subtractive hybridization and complementary DNA array were used. Real-time polymerase chain reaction, Western blotting, and immunohistochemistry were used to evaluate the expression of inhibitor of DNA binding/ differentiation 2 (ID-2). To investigate the function of ID-2 in RASFs, cells were transfected either with ID-2 vector or with ID-2-specific small interfering RNA.Results. EF5 staining showed the presence of hypoxia in arthritic joints, particularly at sites of synovial invasion into bone. Differential expression analysis revealed that ID-2 was strongly induced by hypoxia in RASFs. Immunohistochemical analysis of CIA mouse synovium and human RA synovium showed a strong expression of ID-2 by RASFs at sites of synovial invasion into bone. Overexpression of ID-2 in RASFs significantly induced the expression of several factors promoting osteoclastogenesis. The biologic relevance of the potent osteoclastogenesis-promoting effects was shown by coculture assays of ID-2-overexpressing RASFs with bone marrow cells, leading to an increased differentiation of osteoclasts from bone marrow precursors.Conclusion. The data show that hypoxic conditions are present at sites of inflammation and synovial invasion into bone in arthritic synovium. Hypoxiainduced ID-2 may contribute to joint destruction in RA patients by promoting synovial fibroblast-dependent osteoclastogenesis.

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Articular Cartilage Endurance and Resistance to Osteoarthritic Changes Require Transcription Factor Erg

Ohta

Okabe

Larmour

et al. 2015

Arthritis & Rheumatology

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Objective To determine whether and how transcription factor Erg participates in the genesis, establishment and maintenance of articular cartilage. Methods Floxed Erg mice were mated with Gdf5-Cre mice to create conditional mutants lacking Erg in their joints. Mutant and control joints were subjected to morphological and molecular characterization and also experimental osteoarthritis (OA) surgery. Gene expression, promoter reporter assays and gain- and loss-of-function in vitro tests were used to characterize molecular mechanisms of Erg action. Results Conditional Erg ablation did not elicit obvious changes in limb joint development and overall phenotype in juvenile mice. Over aging, however, mutant joints became spontaneously deranged and exhibited clear OA-like phenotypic defects. Mutant joints in juvenile mice were more sensitive to surgically induced OA and became defective sooner than operated control joints. Global gene expression data and other studies identified PTHrP and lubricin as possible downstream effectors and mediators of Erg action in articular chondrocytes. Reporter assays using control and mutated promoter/enhancer constructs did indicate that Erg acted on ets DNA binding sites to stimulate PTHrP expression. ERG was up-regulated in severely affected areas in human OA articular cartilage, but remained barely appreciable in less affected cartilage areas. Conclusion The study shows for the first time that Erg is a critical molecular regulator of articular cartilage’s endurance over postnatal life and ability to mitigate spontaneous and experimental OA. Erg appears to do so through its regulation of PTHrP and lubricin expression, factors known for their protective roles in joints.

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Ets-1 activates parathyroid hormone-related protein gene expression in tumorigenic breast epithelial cells

Cited by 21 publications

References 35 publications

Parathyroid Hormone Related Protein: A Marker of Breast Tumor Progression and Outcome

Parathyroid Hormone Related Protein: A Marker of Breast Tumor Progression and Outcome

Inhibitor of DNA binding/differentiation 2 induced by hypoxia promotes synovial fibroblast–dependent osteoclastogenesis

Articular Cartilage Endurance and Resistance to Osteoarthritic Changes Require Transcription Factor Erg

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