The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

Sundfeldt, Karin; Ivarsson, Karin; Carlsson, Maria; Enerbäck, Sven; Janson, Per Olof; Brännström, Mats; Hedin, Lars O.

doi:10.1038/sj.bjc.6690199

Cited by 88 publications

(76 citation statements)

References 36 publications

(37 reference statements)

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“…Soluble tissue and cells were prepared by homogenisation in a PEbuffer with proteinase inhibitors, analysed for protein content by the method of Lowry and stored at À701C as previously described (Sundfeldt et al, 1999). Briefly, 35 mg of total protein was diluted in a sodium dodecyl suplhate (SDS)-sample buffer and heated before loading on a 1D SDS-polyacrylamide gel (8% Tris-Glycine) or NuPage gel (10%) (NOVEX, San Diego, CA, USA).…”

Section: Immunoblottingmentioning

confidence: 99%

“…Fresh frozen tissues were cryosectioned and fixed in cold acetone for 10 min, air dried and stored at À201C as previously described (Sundfeldt et al, 1999). Briefly, slides were blocked with 5% nonfat milk (NFM) before the addition of primary antibodies to b-catenin (1 : 100), Lef-1 (1 : 100), Lef-1 antiserum (1 : 100), GSK3b (1 : 50), APC-COOH and APC-NH 2 -terminus (1 : 100) and incubated overnight.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

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Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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Beta-catenin is involved in both cell -cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of b-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3b (GSK3b) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed b-catenin, APC, GSK3b and Lef-1. Nuclear staining of b-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of b-catenin and GSK3b, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of b-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of b-catenin could be due to an increased binding to the cadherin -a-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of b-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

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Section: Immunoblottingmentioning

confidence: 99%

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

et al. 2003

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“…Moreover, overexpression of C/EBPb-2 in a human mammary epithelial cell line lead to anchorage independence and invasive properties (Bundy and Sealy, 2003). C/EBPb is highly expressed in colorectal tumors (Rask et al, 2000) and is associated with ovarian tumor progression (Sundfeldt et al, 1999). Furthermore, C/EBPb can interact with cyclin D1 and appears to be important for the unique pattern of altered gene expression in human cancers that overexpress cyclin D1 (Lamb et al, 2003).…”

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confidence: 99%

Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

et al. 2005

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The CCAAT/enhancer binding protein b (C/EBPb) is implicated in the regulation of many different molecular and physiological processes. Mice with a germline deletion of C/EBPb (C/EBPb À/À ) display phenotypes in a multitude of cell types and organ systems, including skin where C/EBPb À/À mice exhibit increased apoptosis in epidermal keratinocytes in response to carcinogen treatment and are completely resistant to carcinogen-induced skin tumorigenesis. To determine the contribution of systemic versus cell autonomous functions of C/EBPb to specific phenotypes, mice with a conditional 'floxed' C/EBPb null allele were generated. Epidermal-specific deletion of C/EBPb was achieved by Cre recombinase expression from a keratin 5 (K5) promoter. Similar to C/EBPb À/À mice, K5-Cre;C/ EBPb fl/fl mice were completely refractory to 7,12 dimethylbenz[a]anthracene (DMBA)-induced skin tumorigenesis and these mice displayed increased DMBA-induced apoptosis in epidermal keratinocytes compared to wild-type mice. In contrast, mice lacking the related gene, C/EBPd, were not resistant to DMBA-induced skin tumorigenesis, indicating a unique role of C/EBPb in skin tumor development. Our findings demonstrate that C/EBPb exerts an essential, keratinocyte-intrinsic role in cell survival in response to carcinogen treatment and the elimination of C/EBPb in keratinocytes is sufficient to confer complete resistance of the skin to chemical carcinogenesis.

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“…An increased expression of C/EBP ß is reported in breast cancer (24), ovarian cancer (25), colorectal cancer (26) and renal cell carcinoma (27). In contrast, downregulated expression has been reported in squamous cell carcinoma (28) and hepatocellular carcinoma (29).…”

Section: Introductionmentioning

confidence: 99%

Increased expression of CCAAT/enhancer binding protein β correlates with prognosis in glioma patients

Homma

Yamanaka²,

Yajima³

et al. 2006

Oncol Rep

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Abstract. C/EBP ß (CCAAT/enhancer binding protein ß) is a transcriptional factor that belongs to the basic region-leucine zipper class DNA-binding proteins and plays a role in cell differentiation and inflammatory reactions. Although high tissue levels of inflammatory cytokines, such as interleukin (IL)-6, IL-8 and transforming growth factor-ß, have been observed in glioma patients, the mechanisms underlying this phenomenon remain to be elucidated. C/EBP ß induces a variety of cytokines and thus may play a role in the pathogenesis of glioma. In this study, we investigated the relationship between C/EBP ß expression, tumor histology, and prognosis in glioma. The expression of C/EBP ß mRNA was examined with quantitative real-time PCR and protein expression was examined with immunohistochemical techniques in 47 glioma tissue samples. Expression of C/EBP ß mRNA and protein was markedly increased in high grade glioma compared with low grade glioma. Patients whose expression of C/EBP ß mRNA and protein in tumor tissue was lower survived longer than those whose expressions were higher. In vitro, C/EBP ß siRNA inhibited glioma cell proliferation and invasion. Moreover, IL-8 production by glioma cells was inhibited by C/EBP ß siRNA transfection. These data suggest that increased expression of C/EBP ß may contribute to the promotion of tumor invasiveness and progression. The data imply that the comparison of C/EBP ß expression could be a prognostic marker for patients with glioma.

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The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

Cited by 88 publications

References 36 publications

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of β-catenin and GSK3β

Conditional ablation of C/EBPβ demonstrates its keratinocyte-specific requirement for cell survival and mouse skin tumorigenesis

Increased expression of CCAAT/enhancer binding protein β correlates with prognosis in glioma patients

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