Cadherins and catenins in breast cancer

Cowin, Pamela; Rowlands, Tracey; Hatsell, Sarah

doi:10.1016/j.ceb.2005.08.014

Cited by 317 publications

(271 citation statements)

References 59 publications

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“…(Figure 4). The E-cadherin (CDH1) gene is hypermethylated and transcriptionally repressed in gastric and breast cancers, myeloid malignancies, and other tumors (Cowin et al, 2005;Aggerholm et al, 2006;Chan, 2006). We observed hypermethylation of the CDH1 CpG island (Figure 4a), corresponding to a 2.19-fold decrease in gene expression (Figure 3).…”

Section: Primary Myeloid Leukemiasmentioning

confidence: 86%

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

et al. 2007

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Cancer cells display an altered distribution of DNA methylation relative to normal cells. Certain tumor suppressor gene promoters are hypermethylated and transcriptionally inactivated, whereas repetitive DNA is hypomethylated and transcriptionally active. Little is understood about how the abnormal DNA methylation patterns of cancer cells are established and maintained. Here, we identify over 20 DNMT3B transcripts from many cancer cell lines and primary acute leukemia cells that contain aberrant splicing at the 5 0 end of the gene, encoding truncated proteins lacking the C-terminal catalytic domain. Many of these aberrant transcripts retain intron sequences. Although the aberrant transcripts represent a minority of the DNMT3B transcripts present, Western blot analysis demonstrates truncated DNMT3B isoforms in the nuclear protein extracts of cancer cells. To test if expression of a truncated DNMT3B protein could alter the DNA methylation patterns within cells, we expressed DNMT3B7, the most frequently expressed aberrant transcript, in 293 cells. DNMT3B7-expressing 293 cells have altered gene expression as identified by microarray analysis. Some of these changes in gene expression correlate with altered DNA methylation of corresponding CpG islands. These results suggest that truncated DNMT3B proteins could play a role in the abnormal distribution of DNA methylation found in cancer cells.

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Section: Primary Myeloid Leukemiasmentioning

confidence: 86%

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

et al. 2007

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“…Thus, larger MTB-IGFIR1 mammary tumors have characteristics of aggressive tumors yet, despite evidence of local invasion, metastatic spread has not been detected. Breast tumor progression has been associated with the downregulation of the cell-cell adhesion molecule E-cadherin (Cowin et al, 2005). MTB-IGFIR1 mammary tumors retained high expression of E-cadherin even in areas of local invasion.…”

Section: Discussionmentioning

confidence: 99%

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

et al. 2006

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Overexpression and hyperactivation of the type I insulinlike growth factor receptor (IGF-IR) has been observed in human breast tumor biopsies. In addition, in vitro studies indicate that overexpression of IGF-IR is sufficient to transform cells such as mouse embryo fibroblasts and this receptor promotes proliferation and survival in breast cancer cell lines. To fully understand the function of the IGF-IR in tumor initiation and progression, transgenic mice containing human IGF-IR under a doxycyclineinducible MMTV promoter system were generated. Administration of 2 mg/ml doxycycline in the animals' water supply beginning at 21 days of age resulted in elevated levels of IGF-IR in mammary epithelial cells as detected by Western blotting and immunohistochemistry. Whole mount analysis of 55-day-old mouse mammary glands revealed that IGF-IR overexpression significantly impaired ductal elongation. Moreover, histological analyses revealed multiple hyperplasic lesions in the mammary glands of these 55-day-old mice. The formation of palpable mammary tumors was evident at approximately 2 months of age and was associated with increased levels of IGF-IR signaling molecules including phosphorylated Akt, Erk1/Erk2 and STAT3. Therefore, these transgenic mice provide evidence that IGF-IR overexpression is sufficient to induce mammary epithelial hyperplasia and tumor formation in vivo and provide a model to further understand the function of IGF-IR in mammary epithelial transformation.

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“…Even if there is no clear evidence for a role of Ncadherin in promoting breast carcinoma progression (Cowin et al, 2005), several studies have demonstrated that N-cadherin expression in breast cancer cells induces the acquisition of mesenchymal properties and facilitates invasion and metastases in experimental models (Hazan et al, 2000;Suyama et al, 2002). In support of these findings, increased N-cadherin levels were found to be associated with the progression of highly invasive micropapillary breast carcinomas (Nagi et al, 2005).…”

Section: Mfg-e8 Promotes Mammary Tumor Growthmentioning

confidence: 95%

MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells

et al. 2011

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Milk fat globule-EGF factor 8 (MFG-E8) is a glycoprotein highly expressed in breast cancer that contributes to tumor progression through largely undefined mechanisms. By analyzing publicly available gene expression profiles of breast carcinomas, we found that MFG-E8 is highly expressed in primary and metastatic breast carcinomas, associated with absent estrogen receptor expression. Immunohistochemistry analysis of breast cancer biopsies revealed that MFG-E8 is expressed on the cell membrane as well as in the cytoplasm and nucleus. We also show that increased expression of MFG-E8 in mammary carcinoma cells increases their tumorigenicity in immunodeficient mice, and conversely, its downregulation reduces their in vivo growth. Moreover, expression of MFG-E8 in immortalized mammary epithelial cells promotes their growth and branching in three-dimensional collagen matrices and induces the expression of cyclins D1/D3 and N-cadherin. A mutant protein unable to bind integrins can in part exert these effects, indicating that MFG-E8 function is only partially dependent on integrin activation. We conclude that MFG-E8-dependent signaling stimulates cell proliferation and the acquisition of mesenchymal properties and contributes to mammary carcinoma development.

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Cadherins and catenins in breast cancer

Cited by 317 publications

References 59 publications

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

Transgenic overexpression of IGF-IR disrupts mammary ductal morphogenesis and induces tumor formation

MFG-E8/lactadherin regulates cyclins D1/D3 expression and enhances the tumorigenic potential of mammary epithelial cells

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