Expression patterns of β-catenin in in situ and invasive breast cancer

Karayiannakis, Anastasios J.; Nakopoulou, Lydia; Gakiopoulou, Hariklia; Keramopoulos, Antonios; Davaris, Panagiotis; Pignatelli, Massimo

doi:10.1053/ejso.1999.1017

Cited by 70 publications

(81 citation statements)

References 20 publications

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“…We have also recently observed that autocrine production of hGH results in increased nuclear -catenin and transactivation of a T-cell factor-responsive promoter in the presence of inhibitors of glycogen synthase kinase 3 (S Mukhina, H C Mertani & P E Lobie, unpublished observations). The expression of -catenin has been reported to be increased in invasive carcinoma of the mammary gland (Karayiannakis et al 2001). Furthermore we have also identified clusterin and the serine/ threonine kinase activin type 1 receptor as two further genes upregulated by autocrine hGH .…”

Section: Discussionsupporting

confidence: 52%

High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland

Raccurt

Lobie²,

Moudilou³

et al. 2002

Journal of Endocrinology

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We have demonstrated and localized human GH (hGH) gene expression in surgical specimens of normal human mammary gland and in proliferative disorders of the mammary gland of increasing severity using sensitive in situ RT-PCR methodology. hGH mRNA identical to pituitary hGH mRNA was first detected by RT-PCR of RNA derived from samples of normal human mammary gland. Cellular localization of hGH gene expression in the normal mammary gland exhibited restriction to luminal epithelial and myoepithelial cells of the ducts and to scattered stromal fibroblasts. We subsequently examined the expression of the hGH gene in three progressive proliferative disorders of the human mammary gland, i.e. a benign lesion (fibroadenoma), a pre-invasive stage (intraductal carcinoma) and an invasive ductal carcinoma. hGH mRNA was readily detected in the tumoral and nontumoral epithelial components and also in cells of the reactive stroma including fibroblasts, myofibroblastic and myoepithelial cells, inflammatory infiltrate lymphocytes and endothelial cells in areas of neovascularization. In all three proliferative disorders examined, the intensity of the cellular labeling observed in both the epithelial and stromal compartments was always stronger compared with that in adjacent normal tissue. hGH protein was also present in significantly higher concentration in extracts derived from proliferative disorders of the mammary gland compared with extracts derived from normal mammary gland. We also examined hGH gene expression in axillary lymph nodes not containing and containing metastatic mammary carcinoma. hGH gene expression was evidenced in metastatic mammary carcinoma cells and in reactive stromal cells by both in situ hybridization and in situ RT-PCR. In contrast, in lymph nodes not containing metastatic mammary carcinoma, hGH mRNA was detected only by use of in situ RT-PCR. Thus, increased expression of the hGH gene in the epithelial component and the de novo stromal expression in proliferative disorders of the mammary gland are suggestive of a pivotal role for autocrine hGH in neoplastic progression of the mammary gland.

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Section: Discussionsupporting

confidence: 52%

High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland

Raccurt

Lobie²,

Moudilou³

et al. 2002

Journal of Endocrinology

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“…In the present study, ß-catenin staining pattern was predominantly membranous in DCIS whereas in the central parts of invasive breast carcinoma it was also localized in the membrane and cytoplasm and absent in the nucleus consistent with other studies (15,16,(26)(27)(28)(29)(30). However, at the invasive front, in advanced tumors, we have observed a loss of plasma membrane ß-catenin accompanied by cytoplasmic accumulation, suggesting that specific signals from the tumor environment may regulate locally the intracellular ß-catenin distribution.…”

Section: ------------------------------------------------------------supporting

confidence: 91%

Concomitant expression of epithelial-mesenchymal transition biomarkers in breast ductal carcinoma: Association with progression

Brentani¹

2009

Oncol Rep

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Abstract. Epithelial to mesenchymal transition (EMT) is a process implicated in cancer progression in which the underlying cellular changes have been identified mainly using in vitro models. We determined the expression of some putative EMT biomarkers including E-cadherin, ß-catenin, zinc finger factor Snail (Snail), transforming growth factor ß1 (TGFß1), TGFß type II receptor (TBRII) and the HGF receptor (c-met) and their possible correlation to progression and overall survival in a series of breast ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). Biomarkers were immunohistochemically determined in 55 IDC specimens from which 21 had lymph node metastases and in 95 DCIS specimens, 46 of these cases associated to invasive carcinoma, in a tissue microarray (TMA). Positive cytoplasmic staining of TGFß1 (78.2%), c-met (43.6%), Snail (34.5%), TBRII (100%), membranous E-cadherin (74.5%) and membranous/cytoplasmic ß-catenin (71%) were detected in the IDC samples. Metastatic lymph node samples displayed similar frequencies. A significant increase of c-met and TGFß1 positivity along DCIS to IDC progression was noted but only TGFß1 positivity was associated with presence of lymph node metastases and advanced stages in IDC. The evaluation of the other EMT markers in DCIS did not show differences in positivity rate as compared to invasive carcinomas. DCIS either pure or associated to IDC showed similar expression of the analyzed biomarkers. All the carcinomas exhibited positive expression of TBRII. Associations between the markers, determined by Spearman's correlation coefficient, showed a significant association between TGFß1 and respectively E-cadherin, ß-catenin and c-met in DCIS cases, but in invasive carcinomas only cadherin and catenin were positively correlated. Kaplan-Meier survival curves revealed that none of the EMT biomarkers analyzed were correlated with survival, which was significantly determined only by clinical and hormone receptor parameters.

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“…Subsequently, sections were incubated overnight at 4 o C with the primary antibody to phospho-b-catenin (polyclonal antibody produced by immunizing rabbits with a synthetic phospho-Ser 33/Ser 37/Thr 41 peptide corresponding to residues around Ser 37 of human b-catenin, #9561, Cell Signaling Technology Inc.) at a dilution of 1:50. In order to test manufacturing company's assurance that the used antibody does not recognize nonphosphorylated b-catenin, we performed immunohistochemistry with phospho-b-catenin antibody in cases with known positivity for b-catenin, which had been studied in the past 20 and we ascertain that the staining pattern for the two antibodies was completely different. After rinsing in TBS, sections were incubated with biotinylated antirabbit secondary antibody (Vector Labs, Burlingame, CA, USA) for 30 min at room temperature and then incubated with avidin-biotinylated peroxidase complex (Vectastain Elite ABC Kit, Vector Labs) for 30 min.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Study of phospho-β-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome

et al. 2006

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b-Catenin has a crucial role in cell-cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated b-catenin, as well as its relation to the tumors' phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the detection of phospho-b-catenin, ER, PR, c-erbB-2, p53, Ki-67, bcl-2, uPAR and TIMP-1. For each case, a phospho-b-catenin index was determined by image analysis. Phospho-b-catenin staining was detected in the cytoplasm and the nucleus of the malignant cells. Cytoplasmic phospho-b-catenin was statistically higher in carcinomas of smaller tumor size (P ¼ 0.030), lower stage (P ¼ 0.026), decreased Ki-67 and high c-erbB-2 immunoreactivity (P ¼ 0.052 and P ¼ 0.037, respectively). Nuclear phospho-b-catenin showed a parallel correlation with ER and ERb (P ¼ 0.022 and P ¼ 0.043, respectively), bcl-2 (P ¼ 0.042), uPAR in cancer cells (P ¼ 0.041) and TIMP-1, although the correlation was borderline (P ¼ 0.066). Cytoplasmic phospho-b-catenin was found to be independently correlated with prolonged disease-free and overall survival (P ¼ 0.046 and P ¼ 0.002, respectively), whereas nuclear localization was correlated with a shortened overall survival (P ¼ 0.046). In conclusion, phospho-b-catenin may have a different involvement in invasive breast carcinomas, according to its subcellular distribution. Nuclear localization seems to be related to an aggressive tumor phenotype, negatively affecting patients' overall survival, whereas cytoplasmic localization is associated with a favorable tumor phenotype and a longer disease-free and overall survival.

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Expression patterns of β-catenin in in situ and invasive breast cancer

Cited by 70 publications

References 20 publications

High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland

High stromal and epithelial human gh gene expression is associated with proliferative disorders of the mammary gland

Concomitant expression of epithelial-mesenchymal transition biomarkers in breast ductal carcinoma: Association with progression

Study of phospho-β-catenin subcellular distribution in invasive breast carcinomas in relation to their phenotype and the clinical outcome

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